Diabetes Mellitus, Type 2
November 9, 2015
Alizé Pharma has reported positive results
from a phase Ib trial of AZP-531 in type 2
diabetes (T2D). The trial was the last stage in
an overall phase I program performed in 112
healthy volunteers, obese subjects and T2D
patients. The T2D trial was a double-blind 14-
day multiple ascending dose study. The aim
of the trial was to assess the effect of three
doses of AZP-531 v. placebo in a total of 36
uncontrolled T2D patients treated with metformin
as a single agent. The results showed
an improvement in the metabolic status of
patients in all groups, including placebo,
suggesting a study effect in an uncontrolled
T2D patient population. Notwithstanding
this study effect, there was a better metabolic
improvement with AZP-531. In particular, at
the highest doses being studied (60mcg/kg
QD and 30mcg/kg BID), HbA1c was significantly
decreased with a mean decrease of
-0.4% in 14 days (p<0.01 v. baseline). Body
weight also significantly decreased at the
highest dose (60mcg/kg QD) with a mean
decrease of -2.1kg in 14 days (p<0.001 v.
baseline). Administration of AZP-531 for 14
days was well-tolerated across all doses. The
single and multiple-dose PK parameters were
comparable to those observed in healthy
and obese study populations from previous
June 15, 2015
Ligand Pharmaceuticals issued results from a phase Ib trial of LGD-6972 for type 2 diabetes mellitus. In this randomized, double-blind, placebo-controlled trial, LGD-6972 was administered in sequential increasing oral doses daily over two weeks to 48 healthy subjects and subjects with type 2 diabetes. Plasma levels increased linearly with LGD-6972 dosage, and the pharmacokinetic profiles were comparable between normal and type 2 diabetes subjects, supporting once-daily dosing. LGD-6972 lowered fasting plasma glucose in normal subjects and in subjects with type 2 diabetes. Glucose was reduced throughout the 14-day dosing period. Baseline adjusted glucose values showed dose-dependent effects of LGD-6972 in type 2 diabetic subjects with a maximal decrease of 60mg/dL. LGD-6972 tested at 5mg, 10mg and 15mg was safe and well-tolerated with no clinically significant or dose-dependent changes. There were no serious adverse events and no study discontinuations. Ligand is preparing to initiate a phase II trial with LGD-6972 in 2016
December 22, 2014
Poxel reported results of a phase IIb study
of Imeglimin for the treatment of type 2
diabetes. The phase IIb trial assessed the
efficacy and safety profile of four doses of
Imeglimin in 382 patients after 24-week
treatment. In addition to the HbA1C and
FPG reductions obtained with the 1,500mg
dose, the number of responders (defined
as patients achieving an HbA1C below 7%
at the end of the treatment) was statistically
significant (p=0.005) and no patient
required rescue therapy (p=0.01) during the
trial’s duration. The trial achieved its primary
endpoint of HbA1c reduction v. placebo
(p<0.001) and significant decrease in FPG
(Fasting Plasma Glucose) (p<0.006) at a dose
of 1500mg, which will be the dose Poxel
will advance into a phase III development
program. The overall safety and tolerability
profile was positive in all Imeglimin groups,
with a similar overall incidence of adverse
events between treatment groups and
placebo group. The trial reported no serious
adverse events related to the treatment with
August 18, 2014
Biodel released phase IIa results comparing
BIOD-531 to Humalog Mix 75/25 and Humulin
R U-500 in patients with type 2 diabetes with
moderate insulin resistance. A single dose of
BIOD-531 administered immediately before
breakfast achieved significantly lower mean
glucose concentrations than Humalog Mix
75/25 administered immediately before
breakfast. The mean glucose concentration after
breakfast was 167.8 ± 10.4mg/dl with BIOD-531
treatment compared to 205.1 ± 8.3mg/dl with
Humalog Mix 75/25 treatment (p<0.001). Premeal
BIOD-531 was associated with an average
glucose concentration of 177.8 ± 11.9mg/dl
compared to 225.1± 10.7mg/dl with Humalog
Mix 75/25 treatment (p<0.001). Mean glucose
concentrations after the standardized breakfast
were 167.8 ± 10.4mg/dl with BIOD-531
treatment compared to 193.1 ± 8.3mg/dl with
Humulin R U-500 treatment (p=0.006). Mean
glucose concentrations were 177.8 ± 11.9mg/
dl with BIOD-531 treatment compared to 197.2
± 8.8mg/dl with Humulin R U-500 treatment
(p=0.042). Over the course of the entire day of
observation, glucose concentrations were in
the target range of 70-180mg/dl 46.3 ± 8.4% of
the time with BIOD-531 treatment compared to
29.1 ± 6.1% of the time with Humulin R U-500
treatment (p=0.032). Post-meal administration
of BIOD-531 v. pre-meal administration of Humalog
Mix 75/25 and pre-meal administration of
Humulin R U-500 BIOD-531 dosed 20 minutes
after the start of the standardized breakfast also
resulted in a superior glucose control compared
to either Humalog Mix 75/25 or Humulin R
U-500 dosed prior to the meal. Mean glucose
concentrations were 178.3 ± 11.2mg/dl for
post-meal BIOD-531 treatment compared to
225.1 ± 10.7 for pre-meal Humalog Mix 75/25
treatment (p<0.001). The percentage within
the 70-180mg/dl target range was 46.2 ± 7.6%
for post-meal BIOD-531 treatment compared to
20.6 ± 5.9% for pre-meal Humalog Mix 75/25
treatment (p=0.003) and 29.1 ± 6.1% for premeal
Humulin R U-500 (p=0.040).
July 28, 2014
Janssen R&D issued result of a 104-week,
phase III study of INVOKANA (canagliflozin)
in patients aged 55 to 80 years with type 2
diabetes. The randomized, double-blind study
showed INVOKANA 100mg and 300mg, compared
to placebo, provided greater reductions
in blood glucose (A1C) and greater reductions
in secondary endpoints of fasting plasma glucose,
body weight and systolic blood pressure.
After 104 weeks, levels of A1C, the primary
endpoint, were significantly reduced with INVOKANA
100mg and 300mg, respectively, relative
to placebo: -0.49% (95% confidence interval
[CI] -0.65, -0.32) and -0.60% (CI -0.77, -0.44).
The percent of patients reaching the A1C goal
level of less than 7% was 15.6% (100mg: CI
7.2, 24.0) and 21.7% (300mg: CI 13.0, 30.3).
INVOKANA 100mg and 300mg, respectively,
reduced body weight -2.3% (CI -3.1, -1.6) and
-3.2% (CI -4.0, -2.4). INVOKANA 100mg and
300mg, respectively, reduced fasting plasma
glucose: -21.4mg/dL (CI -28.5, -14.2) and
-23.4mg/dL (CI -30.6, -16.2). INVOKANA 100mg
and 300mg, respectively, reduced systolic
blood pressure by -5.8mm Hg (CI -8.0, -3.5 and
-7.5mm Hg (CI -9.8, -5.2).
June 30, 2014
Eli Lilly reported results of two phase III trials of once-weekly dulaglutide 1.5mg for type 2 diabetes. Results showed that once-weekly dulaglutide
1.5mg provided superior blood sugar control at 52 and 78 weeks. Significantly more dulaglutide 1.5mg-treated patients reached target HbA1c levels of less than 7%. Further, at the 26-week primary endpoint, significantly more dulaglutide-treated patients reached target
HbA1c levels of less than 7%, and patients treated with the dulaglutide-mealtime insulin lispro combination had 30% less total insulin dose. The 0.75mg dose also had a lower rate of hypoglycemia compared to insulin glargine. Adverse events were similar for dulaglutide-treated
patients in both studies. The most frequently reported events were gastrointestinal-related. Dulaglutide has been submitted to the FDA, the EMA and other regulators for approval.
April 28, 2014
Islet Sciences issued results of two phase IIb
studies of remogliflozin etabonate for type 2
diabetes. Both were multicenter, randomized,
double-blind, placebo-controlled, pioglitazone-
controlled, 12-week trials. At week 12,
twice-daily dosing of remogliflozin etabonate
produced a statistically significant trend in dose
response for change from baseline (p<0.001)
with changes in HbA1c ranging from -1.0% to
-1.4%. Once-daily dosing demonstrated a trend
in dose response for change from baseline
in HbA1c above the lowest dose (p< 0.047)
with changes in HbA1c ranging from -0.5% to
-0.8%. Decreases from baseline for FPG were
statistically and significantly different from
placebo in all treatment groups. A statistically
significant decrease in body weight (1.36kg to
3.51kg) from baseline was seen in all twice-daily
remogliflozin etabonate treatment groups by
week 12 v. placebo and a statistically significant
decrease in body weight v. placebo (1.44kg to
1.51kg) from baseline was seen in all once-daily
remogliflozin etabonate groups above the
December 16, 2013
Mesoblast reported results of a phase II
trial of Mesenchymal Precursor Cells
(MPCs) in patients with type 2 diabetes.
The phase II, randomized, single-blind,
placebo-controlled, dose-escalation trial
was conducted across 18 sites in the U.S.
The trial evaluated the effects of a single
intravenous infusion of 0.3, 1 or 2 million
MPCs/kg or placebo over 12 weeks in 61
patients with a mean diabetes duration
of 10 years. The highest dose showed the
greatest overall reduction in HbA1c, with
a peak decrease of 0.4% at eight weeks
compared with placebo (p<0.05), and a
decrease of 0.3% at 12 weeks. In the less
well-controlled subjects, as defined by a
baseline HbA1c greater than or equal to
8.0%, a 0.6% decrease in HbA1c was seen
at eight weeks in the high-dose cohort
compared with placebo. In those with
baseline HbA1c less than 8%, a target
of HbA1c less than 7% at week 12 was
achieved in 63% (5/8) of high-dose treated
subjects compared with 0/7 placebo
controls (p<0.05). The MPCs were safe and
well-tolerated with no treatment-related
adverse events, meeting the trial’s primary
Sanofi released results of a phase II trial
of Lantus (insulin glargine [rDNA origin]
injection) for the treatment of type 2
diabetes. The trial included patients who
failed to control their blood sugar levels
on previous basal insulin and oral medication,
together with a long duration of disease
and high body mass index (BMI). The
study randomized 811 participants (1:1)
to U300 (n=404) or Lantus (n=407) once
daily in the evening, while continuing oral
anti-diabetics. EDITION II met its primary
endpoint by showing similar reductions
in HbA1c from baseline between U300 and
Lantus at six months [least squares mean
change -0.57% (0.09) and -0.56% (0.09),
respectively; difference -0.01% (95%
CI: -0.14 to +0.12)] in people with type
2 diabetes who had challenging baseline
characteristics (mean age of study
participants: 58.2 years; duration of type 2
diabetes: 12.6 years; BMI: 34.8kg/m2;
HbA1c: 8.24%; basal insulin dose: 0.67U/kg
at baseline). The percentage of participants
with severe or confirmed (defined
by plasma glucose less than or equal to
70mg/dL) nighttime low blood sugar
levels (nocturnal hypoglycemia) from
month three to six was significantly lower
with U300 v. Lantus [21.6% v. 27.9%; relative
risk (RR) 0.77 (95% CI: 0.61 to 0.99);
p=0.038]. Over the six-month treatment
period, the incidence of any nocturnal
hypoglycemia (% of participants with
greater than or equal to one event) was
lower with U300 v. Lantus [30.5% v. 41.6%;
RR 0.73 (95% CI: 0.60 to 0.89)] as was the
incidence of any hypoglycemic event at
any time of the day (over a 24-hour
period) [U300: 71.5%; Lantus: 79.3%; RR
0.90 (95% CI: 0.84 to 0.97)].
November 18, 2013
Elcelyx Therapeutics reported results of
a 12-week phase IIb study of NewMet, a
delayed-release formulation of metformin
for the treatment of patients with type 2
diabetes. The randomized, 240-patient, multicenter,
double-blind, dose-finding trial evaluated
NewMet once-daily doses of 1000mg,
800mg and 600mg compared to placebo.
There also were two unblinded reference
arms with Glucophage XR dosed once-daily
at 1000mg and 2000mg. All NewMet arms
showed efficacy comparable to or greater
than 1000mg of Glucophage XR. The NewMet
1000mg dose was approximately 50% more
effective than 1000mg of Glucophage XR and
approximately 70% as effective as 2000mg of
Glucophage XR. A dose response trend was
observed across the three NewMet doses,
indicating higher doses of NewMet may
provide greater efficacy. All doses of NewMet
and Glucophage XR prevented the rise in
HbA1c seen with placebo due to washout
of previous anti-diabetic medications. All
doses of NewMet and Glucophage XR were
well-tolerated and there were no meaningful
weight changes observed.
October 14, 2013
AstraZeneca and Bristol-Myers Squibb released results from a phase III study evaluating dapagliflozin in adult patients with type 2 diabetes. The 24-week, phase III, randomized, double-blind, placebo- controlled study with an ongoing 28-week extension was designed to evaluate the efficacy and safety of dapagliflozin in patients with type 2 diabetes with inadequate glycemic control on combination therapy with metformin plus sulfonylurea. The study included 216 adult patients with type 2 diabetes with inadequate glycemic control (HbA1c=7.0% and 10.5%) receiving metformin (1500mg QD) and a maximum tolerated dose of sulfonylurea (at least half the maximum label dose for eight weeks). Patients were randomized to receive dapagliflozin 10mg (n=108) or placebo (n=108). At the end of 24 weeks, patients treated with dapagliflozin 10mg added to metformin plus sulfonylurea demonstrated significantly greater improvements in glycemic control compared to those who received placebo, with a mean change from baseline in HbA1c of -0.86% (95% Confidence Interval [CI]: -1.00, -0.72) in the dapagliflozin group v. -0.17% (95% CI: -0.31, -0.02) in the placebo group (p-value). Significant improvements also were observed in seated systolic blood pressure (SBP) at eight weeks in patients treated with dapagliflozin compared to placebo. A resubmission of the NDA for dapagliflozin was accepted for review by the FDA.
October 7, 2013
Eli Lilly issued positive results of a phase III trial of dulaglutide, an investigational, long-acting glucagon-like peptide 1 (GLP-1) receptor agonist being studied as a onceweekly treatment for type 2 diabetes. The randomized, 52-week, placebo-controlled comparison of the effects of dulaglutide and exenatide twice-daily on glycaemic control in patients with type 2 diabetes on metformin and pioglitazone was conducted in 978 patients dosed with dulaglutide 1.5mg, once weekly. Results showed improvements in HbA1c levels and weight reductions. Dulaglutide-treated patients also demonstrated significant improvements compared to baseline and exenatide twice-daily in perceived hyperglycaemia scores (using DTSQ) at 26 and 52 weeks. Significant improvements also were seen compared to baseline at one year, with no significant differences between dulaglutide and exenatide twice daily. Lilly expects to submit dulaglutide to regulatory authorities in 2013.
September 30, 2013
Takeda Pharmaceutical issued results of a global, randomized, double-blind, placebo-controlled clinical trial of alogliptin in 5,380 patients with type 2 diabetes and a recent acute coronary syndrome (ACS) (within 15 to 90 days prior to randomization). Patients were followed for a median of 18 months and up to 40 months; 71.4% of patients received 25mg, 25.7% received 12.5mg and 2.9% received 6.25mg daily. Alogliptin doses were adjusted according to renal function: estimated glomerular filtration rate (eGFR) by the Modification in Diet in Renal Disease formula ≥ 60ml/min, 25mg daily; < 60ml/min but ≥ 30ml/min, 12.5mg daily; and < 30ml/min, 6.25mg daily. The mean change from baseline in HbA1c was -0.33% and 0.03% in the alogliptin and placebo groups, and the least square means difference in HbA1c between alogliptin and placebo was -0.36% (95% CI, -0.43, -0.28, p<0.001). Testing of the secondary composite endpoint of CV death, myocardial infarction, stroke and unstable angina with urgent revascularization showed no difference in rates on alogliptin v. placebo (12.7% v. 13.4%; hazard ratio, 0.95; one-sided repeated CI bound, 1.14).
August 26, 2013
Boehringer Ingelheim Pharmaceuticals and Eli Lilly released results of a phase III study of dipeptidyl peptidase-4 (DPP-4) inhibitor linagliptin (TRADJENTA) for the treatment of type 2 diabetes (T2D). The 24-week, double-blind, parallel-group, multinational study was conducted in 33 centers in five countries (Australia, Canada, Denmark, The Netherlands and Sweden). A total of 241 elderly people (=70 years; mean age, 74.9 years) with T2D were randomized to receive linagliptin 5mg (n=162) or placebo (n=79), in addition to existing glucose-lowering drugs (i.e. metformin and/or sulfonylurea and/or basal insulin). Key results from the study showed that the mean change from baseline in HbA1c with linagliptin was -0.64% (p<0.0001) after 24 weeks, which showed superiority v. placebo, adjusted for a mean 0.04% HbA1C increase for placebo. In addition, analysis of a secondary endpoint showed that the placebo-adjusted mean reduction in fasting plasma glucose from baseline with linagliptin was -20.7mg/dL (-1.15 mmol/L; p<0.0001). The percentage of people with any adverse event was the same in both treatment groups (75.9%).
MannKind reported results of a phase III study of AFREZZA Inhalation Powder in patients with type 2 diabetes. The study was a double-blind, placebo-controlled study involving 353 patients with type 2 diabetes whose disease was inadequately controlled on metformin with or without a second or third oral medication. Patients were studied at sites in the U.S., Russia, Ukraine and Brazil. After a six-week run-in period, patients entered a 24-week treatment period in which they were randomized to one of two groups where, in addition to their oral medication, they received either AFREZZA Inhalation Powder (177 patients) or Technosphere Inhalation Powder (placebo, 176 patients). Mean A1c levels decreased by 0.82% in the AFREZZA group compared to a decrease of 0.42% in the comparator oral-therapy group, a statistically significant (p<0.0001) change. The incidence of serious adverse events was lower in the AFREZZA group (2.8%) compared to the comparator oraltherapy group (5.1%).
July 1, 2013
Boehringer Ingelheim Pharmaceuticals and Eli Lilly released results from a phase III trial of empagliflozin for the treatment of drug-naive adults with type 2 diabetes (T2D). The 24-week, randomized, double-blind, placebo-controlled trial enrolled 14,500 multinational patients. Patients were randomized to receive empagliflozin 10mg (n=224) or 25mg per day (n=224), sitagliptin 100mg per day (n=223) or placebo (n=228) for 24 weeks. Patients with average blood glucose (HbA1c) more than 10% (n=87) received open-label empagliflozin 25mg per day for 24 weeks. Results of the primary endpoint showed placebo-adjusted reductions in HbA1c from baseline to week 24 of 0.74% and 0.85% (p<0.001) for the 10mg and 25mg doses, respectively. After 24 weeks, body weight decreased by 4.25 lbs and 4.74 lbs (p<0.001) in patients treated with empagliflozin 10mg and 25mg, respectively, versus placebo. Changes in diastolic blood pressure were statistically significant for the empagliflozin 25mg treatment group only (1.9 mmHg reduction v. 0.5 mmHg reduction for placebo, p=0.030).
May 13, 2013
Esperion Therapeutics reported results from a phase II trial of ETC-1002 for type 2 diabetes and hypercholesterolemia. This randomized, double-blind, placebo-controlled, parallel-group study enrolled 60 patients with type 2 diabetes (HbA1C 7-10%), a body mass index of 25-35kg/m2, and LDL-C≥100mg/dL. Subjects received ETC-1002 80mg for two weeks followed by ETC-1002 120mg for two weeks, or placebo for four weeks, and were treated in an inpatient unit where their diet and lifestyle were controlled. Results showed after two weeks of treatment with 80mg of ETC-1002, LDL-C was reduced by an average of 32% (p<0.0001), while after an additional two weeks of 120mg of ETC-1002, LDL-C was reduced by an average of 43% (p<0.0001) compared with 6% and 3% reductions, respectively, for those patients treated with placebo. ETC-1002 also significantly reduced non-HDL-C (by 30%; p=0.0001) and high sensitivity C-reactive protein (hsCRP) and blood pressure compared with placebo. ETC-1002 had neutral effects on other lipids, including triglycerides and HDL-C. The drug was well tolerated. The most frequent adverse events were headache, hyperglycemia, constipation, arthralgia, dry eye and viral upper respiratory tract infection. Esperion is currently evaluating ETC-1002 in multiple phase II trials in more targeted patient populations.
April 22, 2013
Eli Lilly released results from a phase III trial of dulaglutide for the treatment of type 2 diabetes. This randomized, 52-week, open-label study, AWARD-4, enrolled 884 patients with type 2 diabetes. Subjects received 1.5mg dulaglutide once-weekly plus insulin lispro, or insulin glargine plus insulin lispro. Primary efficacy endpoints of non-inferiority to insulin glargine, as measured by the reduction of hemoglobin A1c (HbA1c) levels at the 1.5 mg dose, were met. Furthermore, results showed that the dulaglutide and insulin lispro arm demonstrated statistically superior reduction in HbA1c from baseline compared to insulin glargine in combination with insulin lispro at 26 weeks. Dulaglutide was well tolerated. The most frequent adverse events were gastrointestinal-related. Based on these results, Eli Lilly expects to submit dulaglutide to regulatory authorities in 2013.
October 8, 2012
Boehringer Ingelheim and Eli Lilly released pooled analysis of two phase IIb trials of empagliflozin in conjunction with metaformin for the treatment of type 2 diabetes (T2D). These randomized, double blind, placebo-controlled studies enrolled 903 patients. Subjects received 10mg or 25mg of empagliflozin plus metaformin, or placebo for 12 weeks. Results showed both dosages reduced the systolic blood pressure (SBP) and were statistically significant compared to placebo. SBP was reduced by 3.8mmHg and 4.5mmHg in the empagliflozin 10mg and 25mg arms, respectively, versus 1.2mmHg for placebo. Mean SBP at baseline of 131.3mmHg and 132.5mmHg were observed with empagliflozin 10mg and 25mg, respectively, versus 134.3mmHg with placebo. In patients with higher SBP at baseline (>140 mmHg), mean reductions of 17.0mmHg and 13.4mmHg were observed with empagliflozin 10mg and 25mg, respectively, and 10.4mmHg with placebo. The drug was well tolerated. The most frequent adverse events were urinary tract infection and genital infections. Empagliflozen is being investigated in 12 different ongoing multinational studies, with filing planned in the U.S. and Europe in 2013.
Merck issued results for a phase IIb trial of MK-3102 for the treatment of type 2 diabetes. This multi-center, randomized, double blind, placebo-controlled, dose-ranging study enrolled 685 patients with a mean baseline HbA1c of approximately 8%. Subjects received MK-3102 0.25mg, 1mg, 3mg, 10mg or 25mg once-weekly, or placebo, for 12 weeks. Results demonstrated MK-3102 significantly reduced HbA1c compared to placebo (p<0.001) from baseline across all doses. The placebo-adjusted reduction from baseline in HbA1c was 0.71% with MK-3102 25mg; 0.67% with 10mg; 0.49% with 3mg; 0.50% with 1mg; and 0.28% with 0.25mg. The drug was well tolerated. Based on these data, Merck is initiating a phase III study.
August 13, 2012
TWi Biotechnology reported results from a phase II trial of AC-201 for the treatment of type 2 diabetes (T2D). This multinational, dose-ranging study enrolled 259 patients whose T2D was uncontrollable on up to three oral medications. Subjects received AC-201 25mg, 50mg, 75mg or placebo twice daily for 24 weeks. In the intent-to-treat population, AC-201 showed placebo-corrected reductions in HbA1c of 0.20%, 0.29%, and 0.35% (p<0.05), respectively. In the perprotocol population, the placebo-corrected reduction in HbA1c was 0.37%, 0.42%, and 0.49%, respectively. AC-201 was well tolerated up to 75mg. The most frequent adverse event was diarrhea. TWi Biotechnology did not note its plans for AC-201.
July 16, 2012
GlaxoSmithKline issued results from a phase III trial of albiglutide versus sitagliptin for the treatment of renal impairment. This double-blind, active-controlled, parallel-group, multicenter study, Harmony 8, enrolled patients with type 2 diabetes. Subjects received recommended doses of either albiglutide of sitagliptin for 52 weeks. At the 26-week primary endpoint, albiglutide showed clinically and statistically significant reductions in HbA1c from baseline (8.08% for albiglutide and 8.22% for sitagliptin) and superiority versus sitagliptin (reduction of 0.83% vs 0.52%; p<0.0001 for non-inferiority and p=0.0003 for superiority). At the primary endpoint, weight loss was significantly greater in the albiglutide group than the sitagliptin group (-0.79kg vs -0.19kg; p=0.0281). During the full 52-week treatment period, albiglutide was generally well tolerated. The most frequent adverse events were diarrhea (albiglutide 10%, sitagliptin 6.5%), nausea (4.8%, 3.3%) and vomiting (1.6%, 1.2%). With these data now available, GSK intends to commence global regulatory submissions for its investigational glucagon-like peptide-1 (GLP-1) receptor agonist albiglutide for the treatment of type 2 diabetes in early 2013.
July 2, 2012
Lexicon Pharmaceuticals reported results from a phase IIb trial of LX4221 for the treatment of type 2 diabetes. The multi-center, randomized, dose-ranging study enrolled 299 patients who were concurrently being treated with metformin. Subjects received LX4221 75mg once daily (QD), 200mg QD, 200mg twice daily (BID) or 400mg QD, or placebo for 12 weeks. Top-line results showed that patients in the LX4211 treatment arms had mean HbA1C reductions from baseline of 0.43%, 0.52%, 0.79% and 0.95%, respectively (p<0.001 for all treatment arms). In patients randomized to placebo, HbA1C decreased by 0.09%. LX4211 treatment also produced significant reductions in body weight and blood pressure. The drug was well-tolerated and safe. Adverse events were similar to placebo. Based on these data, Lexicon plans to initiate a phase III trial of LX4221 in the first half of 2013.
June 18, 2012
Bristol-Myers Squibb and AstraZeneca reported results from a phase III trial of dapagliflozin for the treatment of type 2 diabetes. This multicenter, randomized, double-blind, placebo-controlled, parallel group study enrolled 447 adult patients with inadequate glycemic control who were on a stable dose of sitagliptin. Subjects in stratum one received dapagliflozin 10mg or placebo added to sitagliptin 100mg/d. Patients in stratum two received dapagliflozin 10mg or placebo added to sitagliptin 100mg/d plus metformin ≥1500mg/d. Both stratums were conducted for 24 weeks, plus a 24-week blinded extension. Subjects (n≡223) receiving dapagliflozin 10mg plus sitagliptin with or without metformin demonstrated significantly greater improvements in glycemic control at 24 weeks compared to subjects (n≡224) receiving placebo plus sitagliptin with or without metformin, with a change in baseline in HbA1c of -0.48% (p-value <0.0001, Last Observation Carried Forward [LOCF]). Significant reductions in body weight were observed with dapagliflozin compared to placebo in the entire treatment cohort (-1.89kg, LOCF), stratum one (-1.85kg, LOCF) and stratum two (-1.87kg, LOCF), and were sustained out to 48 weeks. The drug was well tolerated. The most common adverse events were nasopharyngitis, back pain, urinary tract infection, pharyngitis, arthralgia and headache. BMS and AstraZeneca are currently waiting for the European Commission to review dapagliflozin.
June 4, 2012
Boehringer Ingelheim and Eli Lilly issued results from a phase III trial of linagliptin for the treatment of type 2 diabetes. This randomized, placebo-controlled trial enrolled 226 black or African American adult subjects with type 2 diabetes whose blood sugar was not adequately controlled. Subjects received 5mg of linagliptin once-daily or placebo for 24 weeks. The trial met its primary endpoint, showing a significant reduction of hemoglobin A1c (HbA1c or A1C) in 0.88% of subjects treated with linagliptin compared to 0.24% in the placebo group (p≡0.0002). The drug was well tolerated. The most frequent adverse events were hyperglycemia and nasopharyngiti. This is the first published trial of a DPP-4 inhibitor specifically conducted in black or African American adult patients with type 2 diabetes.
January 16, 2012
Lexicon reported results from a clinical trial evaluating LX4211 in combination with sitagliptin (Januvia) for the treatment of type II diabetes. The trial enrolled 18 subjects with type II diabetes who received single doses of either LX4211 (400 mg), sitagliptin (100 mg) or LX4211 plus sitagliptin on Days 1, 8, or 15. Single doses of LX4211 plus sitagliptin produced lower blood glucose levels after meals as compared to treatment with sitagliptin alone (p≡0.012). This enhanced glycemic control was associated with an elevation of active glucagon-like peptide-1 (GLP-1) over treatment with either LX4211 or sitagliptin alone (p<0.001). In addition, LX4211 increased total GLP-1 (p<0.001) and PYY (p≡0.014) with reduced insulin levels (p≡0.025) when dosed with sitagliptin; these effects were not observed with sitagliptin alone.
December 12, 2011
Sanofi released results from a phase III trial of lixisenatide plus Lantus for type II diabetes. This 24-week randomized, double-blind, placebo-controlled study, GetGoal Duo 1, treated 446 type II diabetics with HbA1c >>7% despite oral anti-diabetic treatment. The subjects were randomized to receive either lixisenatide once-daily or placebo, both with Lantus (insulin glargine) and metformin. After 24 weeks the subjects who were treated with lixisenatide in addition to insulin glargine had a significant HbA1c decrease compared with the placebo group (p<0.0001) to a mean value of 6.96%. A significantly higher percentage of subjects in the lixisenatide arm achieved target HbA1c <7.0% compared to the placebo group (56.3% versus 38.5%, p≡0.0001). Lixisenatide also significantly improved 2-hour post-prandial glucose with a mean difference of -3.16 mmol/L (p<0.0001) versus placebo.
November 7, 2011
Dara Biosciences issued results from a phase Ib trial of DB959 for type II diabetes. This randomized, placebo-controlled, double-blind, escalating multiple dose clinical trial enrolled 32 healthy subjects. The subjects received once daily doses of DB959 or placebo for seven sequential days. The overall safety profile was comparable to placebo, demonstrating that DB959 is safe and well-tolerated throughout the 40-fold dose-range tested. Pharmacokinetic data indicated DB959 is likely to meet the target dosing regimen of once-a-day and DB959 will be pharmacologically active in within the dose range utilized in this study.
August 15, 2011
Repros Therapeutics released interim results from a phase II trial of Androxal for hypogonadal men with type II diabetes. Data are from 61 subjects who completed a three month dosing regimen of Androxal 12.5 or 25 mg or placebo. At baseline, mean morning testosterone levels for the three groups were 224.9 ng/dl, 238.2 ng/dl and 233.8 ng/dl for the placebo and Androxal 12.5 and 25 mg arms, respectively. At the end of the three month dosing period the mean morning testosterone levels increased to 234.2 ng/dl, 463.5 ng/dl and 444.7 ng/dl, respectively. Both Androxal arms were highly statistically different from placebo (p<0.0001). In the group of subjects that achieved a morning level of testosterone >450 ng/dl and met the per protocol requirement of BMI <40 (n≡14) a statistically significant reduction in HbA1c was observed compared to placebo (p≡0.02). There was a concurrent reduction in fasting plasma glucose levels in the responding Androxal arms (men > 450ng/dl) of -21 mg/dl compared to the placebo group which exhibited a slight increase of 2.0 mg/dl.
July 18, 2011
Genfit issued results from a phase II trial of GFT505 for type II diabetes. This parallel group, placebo-controlled, double-blind study, GFT505-210-5, enrolled 97 treatment nave subjects. The subjects received GFT505 at 80mg/day or placebo for 12 weeks. GFT505 resulted in a significant reduction in HbA1c levels (-0.4%, p≡0.01), in two hour glycemia (-38 mg/dL; p<0.001), and in the area under the curve for glycemia (-39 mg/dL hour; p<0.001) when compared to baseline values. There was also a reduction in fasting glycemia in the GFT505 group, while this parameter was not altered in the placebo group. In addition, GFT505 treatment lowered plasma triglyceride levels and significantly lowered non-HDL-C, LDL-C and total cholesterol. The level of HDL-C was increased by +15% (p<0.0001) compared to baseline values, but a significant effect was also observed in the placebo group (+11%, p<0.01). Markers of hepatic dysfunction were improved upon GFT505 treatment, with a highly significant reduction in gamma GT levels (-28% vs placebo, p<0.0001).
July 4, 2011
Chemocentryx released results from a phase II trial of CCX140 for the treatment of type II diabetes. This multinational, randomized, double-blind, placebo and active-controlled clinical trial enrolled 159 subjects with type II diabetes on stable doses of metformin. The subjects received once daily doses of CCX140 at 5 mg or 10 mg, open label pioglitazone 30 mg or placebo for a four week dosing period. Daily treatment with CCX140 showed a dose-dependent decrease in fasting plasma glucose through week four. A significant decrease in HbA1c was observed after four weeks of daily treatment with CCX140 10 mg compared to placebo (p≡0.045). CCX140 was safe and well tolerated.
Takeda issued results from a phase II trial of TAK-875 for type II diabetes. This randomized, double-blind, placebo- and active (glimepiride) controlled trial enrolled 426 type II diabetics. The subjects received once-daily treatment with five different doses of TAK-875 (6.25 mg, 25 mg, 50 mg, 100 mg, or 200 mg), glimepiride 2 mg or 4mg once daily or placebo. The treatment duration was 12 weeks. The primary endpoint was the change from baseline in HbA1c levels at week 12. Study results found that all doses of TAK-875 showed significantly greater HbA1c reductions at week 12 versus placebo and the reductions were comparable to glimepiride. When compared to placebo approximately twice as many subjects (33-48%) treated with TAK-875 at 25 mg and above achieved HbA1c less than 7% at week 12; this was similar to glimepiride. The incidence of hypoglycemia was significantly lower for all doses of TAK-875 (2.3%) compared to glimepiride (16.1%) and similar to placebo (3.3%). The treatment was generally well tolerated.
February 7, 2011
Zealand Pharma and Sanofi Aventis reported results from a phase III trial of lixisenatide, for type II diabetes. This randomized, open-label, active-controlled, two-arm parallel-group, multicenter study, GETGOAL-X, was designed to determine if lixisenatide is non-inferior to exenatide (Byetta), the standard of care. The trial enrolled 639 subjects with type II diabetes inadequately controlled by metformin who received lixisenatide once daily or exenatide twice daily, both administered in increasing doses, up to a maximum daily dose of 20microg. The primary endpoint of non-inferiority in HbA1c reduction from baseline was reached. In addition, in the lixisenatide arm there were fewer reports of symptomatic hypoglycemia versus the exenatide arm (2.5% vs. 7.9%; p<<0.05) and fewer hypoglycemia events (8 vs. 48 events, respectively).
November 15, 2010
Arena Pharmaceuticals and Eisai released positive results from a phase III trial of lorcaserin for obesity and type II diabetes. This trial, dubbed BLOOM-DM, enrolled 604 obese and overweight subjects with type II diabetes who were randomized to lorcaserin 10 mg twice daily (BID), lorcaserin 10 mg dosed once daily (QD) or placebo. To expedite enrollment, randomization to the lorcaserin 10 mg QD dose was discontinued after approximately 300 patients were enrolled in the trial. The trial had three primary efficacy endpoints at Week 52: the proportion of patients who lost at least 5% of their baseline body weight; change from baseline in body weight; and the proportion of patients who lost at least 10% of their baseline body weight. All three endpoints were reached with lorcaserin 10 mg BID by producing statistically significant weight loss compared to placebo (p<0.0001). At Week 52: 37.5% of subjects in the lorcaserin arm achieved at least 5% weight loss compared to 16.1% of the placebo arm; subjects treated with lorcaserin achieved mean weight loss of 4.5% (4.7 kg), compared to 1.5% (1.6 kg) for placebo and 16.3% of the lorcaserin arm achieved at least 10% weight loss, compared to 4.4% of the placebo arm.
September 27, 2010
AstraZeneca and Bristol-Myers Squibb issued positive results from a phase III trial evaluating dapagliflozin plus glimepiride (sulphonylurea) for type II diabetes. This 24-week, multicenter, international, randomized, parallel-group, double-blind, placebo-controlled study enrolled 597 type II diabetics with inadequate glycemic control. The subjects were randomized to one of four treatment groups: dapagliflozin 2.5, 5 or 10 mg plus glimepiride or placebo plus glimepiride. The primary endpoint of the study was to assess the change from baseline in HbA1c at 24 weeks. The dapagliflozin plus glimepiride treatment arms showed significant dose-dependent reductions from baseline in HbA1c of -0.58%, -0.63% and -0.82% for dapagliflozin 2.5 mg, 5 mg and 10 mg, respectively compared to -0.13% for placebo plus glimepiride (p<0.0001 for all three treatment arms). Secondary endpoints were also reached, including reductions from baseline in weight loss and the oral glucose tolerance test and improvements in fasting plasma glucose week 24.
July 5, 2010
Intarcia released positive results from a phase II trial of ITCA 650 for the treatment of type II diabetes. This study enrolled 150 subjects with sub-optimally controlled type II diabetes treated with metformin. During the first 12 weeks of the study the subjects received subcutaneous injections of ITCA 650 (20 or 40 mcg/day) or twice daily injections of Byetta, (standard of care) at 5 mcg for four weeks followed by 10 mcg thereafter. Both doses of ITCA650 demonstrated substantial reductions in HbA1c and body weight during the 12 weeks of treatment. The change from baseline HbA1c was similar between the treatment arms: -0.96, -1.04 and -0.82 for the ITCA650 arms and the Byetta arm, respectively. The mean percent change in body weight at week 12 was -0.87%, -2.62% and -1.54%, respectively. In addition, subjects receiving either dose of ITCA 650 experienced greater improvement in their quality of life compared to those receiving twice daily injections of Byetta.
June 21, 2010
Amylin, Eli Lilly and Alkermes reported positive results from a phase III study of Bydureon (exenatide extended-release) for the treatment of type II diabetes. This double-blind study, DURATION-4, enrolled 820 treatment-nave subjects who were not achieving adequate A1C control with diet and exercise. The subjects received Bydureon (2 mg, once per week); metformin (dose escalated up to 2,500 mg/day); Actos (dose escalated up to 45 mg/day) and Januvia (100 mg/day. The primary endpoint was reduction in A1C. After 26 weeks of treatment, subjects randomized to Bydureon had a reduction in A1C of 1.5 percentage points from baseline, which was significantly greater than the reduction of 1.2 percentage points for Januvia. Subjects in the metformin arm had a reduction in A1C of 1.5 percentage points, and those receiving Actos had a reduction of 1.6 percentage points. Treatment with Bydureon resulted in an average weight loss of 4.5 pounds, which was statistically significantly greater than the average 1.7 pounds lost with Januvia and the average 3.3 pounds gained with Actos.
April 26, 2010
Phenomix released positive results from a phase III trial of dutogliptin for the treatment of type II diabetes. This 24-week, international, randomized, double-blind, parallel group, placebo-controlled study (PROT301) enrolled 542 subjects with moderately elevated baseline hemoglobin A1c (HbA1c) levels. The subjects received dutogliptin 400mg or 200mg once daily or placebo. The primary endpoint was statistically significant reductions of HbA1c versus placebo at week 24. Reductions in HbA1c corrected for placebo effects were 0.59% for the 400mg dose (p<0.0001) and 0.28% for the 200mg dose (p<0.0138). Statistical significance was also observed at the 400mg dose for all secondary endpoints, including change from baseline in fasting and peak postprandial plasma glucose, change from baseline in glucose AUC (0-2 hours) after a standard test meal, and percentage of subjects reaching treatment goal of HbA1c of less than 7.0%.
February 1, 2010
Transition issued positive results from a phase II trial of TT-223 for the treatment of type II diabetes. This randomized, double-blind, placebo-controlled, dose-ranging study enrolled 80 subjects who received a daily treatment of TT-223 in addition to their current regimen of oral glucose lowering agents. The once-daily dose of TT-223 was titrated as tolerated to the maximum dose during the first three weeks; this highest tolerated dose was administered for the remaining nine weeks of the treatment period. After the completion of the treatment period, subjects were followed for an additional six months. The subjects who received the highest daily dose of TT-223 for 12 weeks and completed the entire study without adjusting their diabetes therapies experienced a statistically significant reduction in HbA1c of 1.13%, 6 months after completing TT-223 versus a 0.22% HbA1c reduction for placebo. Post prandial and area under the curve glucose showed improvement versus placebo but not against baseline at 3 and 6 months post-treatment. There were no treatment-related serious adverse events.
January 25, 2010
Lexicon issued positive results from a phase II trial of LX4211 for type II diabetes. This four-week, randomized, double-blind, placebo-controlled study enrolled 36 subjects in the U.S. The subjects received either placebo or LX4211, 150 mg or 300 mg, once daily for 28 days. There was a marked decrease in fasting plasma glucose throughout the treatment period in both dose groups, with reductions at week four of 53.4 mg/dl and 65.9 mg/dl in the 150 mg and 300 mg dose groups, respectively, as compared to 15.1 mg/dl for placebo (p≡0.001 and p<0.001, respectively). In the 300 mg dose group, 42% of subjects achieved fasting plasma glucose levels of <105 mg/dl at week four of dosing as compared to placebo (p≡0.037). After four weeks of dosing, average hemoglobin A1c (HbA1c) was significantly reduced by 1.15 in the 150 mg dose group (p≡0.036) and by 1.25 in the 300 mg dose group (p≡0.017), as compared to 0.49 in the placebo group. HbA1c levels were reduced to less than or equal to 7% for half the patients in both dose groups; baseline levels were 8.22%, 8.50% and 8.20% for the 150 mg, 300 mg, and placebo groups, respectively.
January 18, 2010
Dr. Reddy's and RheoScience reported results from a phase III study of balaglitazone for type II diabetes. This randomized, double blind, parallel-group placebo- and active comparator-controlled clinical study (Study 307) enrolled 409 subjects. The subjects received balaglitazone 10mg or 20mg, Pioglitazone 45mg (standard of care) or placebo, each added to a background treatment regimen of stable insulin therapy, for a period of 26 weeks. The primary endpoint was HbA1c reduction. All three active arms (balaglitazone 10mg, 20mg and Pioglitazone 45mg) showed similar levels of efficacy compared to placebo with respect to both HbA1c (0.99 %, 1.11 % and 1.22 %, respectively) and fasting plasma glucose (1.42 mmol/L, 1.80 mmol/L and 1.35 mmol/L, respectively). All three active arms showed good tolerability and adverse event profile, with balaglitazone 10mg demonstrating less water retention, less fat accumulation, lower weight/BMI gain and less bone loss when compared to the Pioglitazone arm.
November 23, 2009
Spherix released positive interim results from a phase III trial of D-tagatose for the treatment of type II diabetes. This double-blind, placebo-controlled study, NEET (Naturlose (D-tagatose) Efficacy Evaluation Trial), planned to enroll 332 treatment-nave subjects in the United States and India. The subjects received D-tagatose as monotherapy as an adjunct to diet and exercise. The primary endpoint, a statistically significant change in HbA1c versus placebo, was reached. Secondary endpoints, including reductions in LDL, HDL, triglycerides, and body mass index compared to baseline, also appeared to reach statistical significance. In addition, The incidences of responders achieving an HbA1c target of <6.5% at 1, 2, 4 and 6 months of treatment were 4%, 13%, 19% and 18% respectively
October 12, 2009
Bristol-Myers Squibb and AstraZeneca reported positive results from a phase III trial of dapagliflozin for the treatment of type II diabetes. This randomized, double-blind, placebo-controlled study enrolled 546 subjects with type 2 diabetes inadequately controlled with metformin alone. After a two-week lead-in phase, subjects were randomized to one of four separate treatment arms: dapagliflozin 2.5 mg, dapagliflozin 5 mg, dapagliflozin 10 mg, or placebo. All arms also received metformin (greater than or equal to 1500 mg/d). The primary endpoint of the study compared mean HbA1c change from baseline for each dapagliflozin treatment arm compared to placebo after 24 weeks. The baseline HbA1c was greater than or equal to 7.0 percent and less than or equal to 10 percent. After 24 weeks, the dapagliflozin 2.5 mg, 5 mg and 10 mg plus metformin treatment arms demonstrated a statistically significant adjusted mean change in HbA1c from baseline of -0.67%, -0.70% and -0.84%, respectively, compared to -0.30% for placebo (p<0.0005 for all treatment arms). Key secondary endpoints were reached as well. The adjusted mean change in fasting plasma glucose (FPG) from baseline at Week 24: -17.8 mg/dL for dapagliflozin 2.5 mg; -21.5 mg/dL for dapagliflozin 5 mg and -23.5 mg/dL /dl for dapagliflozin 10 mg, compared to -6.0 mg/dL for placebo (p<0.005 for all treatment arms). The adjusted percentage of subjects treated with dapagliflozin who achieved HbA1c of less than 7% at 24 weeks was significant for for dapagliflozin 5 mg (37.5%) and dapagliflozin 10 mg (40.6%) compared to 25.9% for placebo (p<0.05). In addition, the change in total body weight in kg showed statistical significance over placebo. At 24 weeks, the change was -2.21 kg for dapagliflozin 2.5 mg, -3.04 kg for dapagliflozin 5 mg and -2.86 kg for dapagliflozin 10 mg, compared to -0.89 kg for placebo (p< 0.0001). Dapagliflozin was generally well tolerated across the treatment arms.
July 6, 2009
Spherix issued positive interim results from a phase II trial of Naturlose for the treatment of type II diabetes. This single-blind, prospective, randomized, multicenter study has enrolled 38 subjects to date. The subjects received Naturlose administered orally with meals three times daily (TID) at three different doses, 2.5, 5.0, and 7.5g for a six month treatment duration. The trial was designed to establish the minimum dose of Naturlose capable of causing a beneficial effect on HbA1c. The primary endpoint was reduction in HbA1c after 6 months; the comparator was the 2.5 g dose. At six months, the subjects in the 7.5 g group experienced an average reduction of 0.3% in HbA1c compared to the 2.5 g group. The 5.0 g group averaged a reduction in HbA1c of 0.05% from the 2.5 g group. Naturlose also decreased the average serum triglycerides by -59 mg/dl by the end of the first month, a decrease from baseline that remained at -41 mg/dl to the end of the six month period. Naturlose also decreased serum LDL by an average -13 mg/dl by the end of the first month, while serum HDL was essentially unchanged (+0.9 mg/dl). The LDL:HDL ratio was improved for two of the three dose groups by an average of 0.3.
June 29, 2009
Glenmark Pharmaceuticals released positive results from a phase IIb trial of melogliptin for the treatment of type II diabetes. This 12-week, randomized, double-blind, placebo-controlled, parallel group study enrolled 494 subjects who received melogliptin 50mg twice daily, 100 mg once daily or placebo. The primary endpoint was the reduction of HbA1c from baseline. Both doses of melogliptin significantly reduced HbA1c from baseline as compared to placebo with a mean average reduction of 0.75% in subjects receiving the 50mg twice daily dose (p<0001) and 0.60 % in subjects receiving the 100 mg once daily dose (p<.0001). In a subgroup of subjects with higher baseline HbA1c of 8.5%-10%, melogliptin reduced HbA1c from baseline as compared to placebo with a mean average reduction of 0.88 % and 1.05 % in the 100mg once daily and 50mg twice daily dosage arms, respectively.
March 30, 2009
Metabasis released positive results from a phase II trial of MB07803 tablets for the treatment of type II diabetes. This randomized, double-blind, placebo-controlled, ascending multiple dose study enrolled 42 subjects with poorly-controlled type II diabetes who received either an oral dose of 50 mg, 200 mg, or 400 mg MB07803 or a matching oral dose of placebo every 12 hours for 14 days. The efficacy endpoint was the change from baseline at Day 14 in the glucose lowering response (determined by the area-under-the-curve, AUC) as measured after administration of the morning dose and during the last six hours of a prolonged 18 hour fast. The results showed that the 6-hour AUC was reduced from -93 (mg.hr/dL) for the placebo treated arm to -236 (p≡0.17), -442 (p≡0.002), and -532 (p≡0.0002 mg.hr/dL for subjects treated with 50 mg, 200 mg and 400 mg arms, respectively. The top two doses also achieved statistical significance in the endpoint of a single point measure of fasting plasma glucose versus placebo (p≡0.002 and p≡0.0002 for 200 mg and 400 mg, respectively). MB07803 was safe at all doses tested and well tolerated up to 200 mg twice-daily.
February 16, 2009
Genaera issued positive preliminary results from a phase Ib trial of trodusquemine for the treatment of type II diabetes and obesity. This placebo controlled, multiple ascending dose study, dubbed Study 102, planned to enroll 21 obese type II diabetic subjects. The subjects will receive three dose levels (3, 6, and 10 mg/m2) of trodusquemine or placebo every three days over a 21 day period. The primary endpoints are safety and multiple dose pharmacokinetics. Secondary outcomes include oral glucose tolerance and insulin sensitivity, satiety and weight loss. Data are from the first cohort (eight doses of 3 mg/m2 over 21 days). Treatment with trodusquemine led to a 9.5% decrease in fasting blood glucose, a 7% decrease in the area under the curve during the oral glucose tolerance test; an 11.3% decrease in serum fructosamine, which is used to monitor short-term (2-3 weeks) blood sugar control; and a 0.4% decrease in hemoglobin A1C (HbA1C), used to monitor longer-term (2-3 months) blood sugar control. Treatment was well tolerated, with no serious adverse events or dose-limiting toxicities reported.
December 15, 2008
ConjuChem issued positive results from two phase II trials of PC-DAC-Exendin-4 for the treatment of type II diabetes. The two Phase II trials were randomized, double-blind, placebo-controlled, multiple dose studies that evaluated the efficacy and safety of three months of weekly or twice-weekly injections of PC-DAC:Exendin-4 in subjects with Type 2 diabetes not adequately controlled by metformin monotherapy. In the first trial, 144 subjects were randomized to one of three parallel treatment groups: a 1.5 mg per week cohort; a 1.5 mg per week cohort titrating to 2 mg per week after one month; and a placebo cohort. In the second trial, 80 subjects were randomized to one of three parallel treatment groups: a 1.5 mg twice-weekly cohort titrating to 2 mg per week after one month; a 3 mg (1.5 mg twice per week) cohort; and a placebo cohort. The primary endpoint, reduction in HbA1c versus both baseline and placebo, was reached with significance for all active treatment groups throughout the treatment period. The most significant reduction was in the 3 mg dose group, a decrease of 1.4% at the end of the treatment period (day 85) was observed. The HbA1c reduction was 0.8% for both the 1.5 mg and 2 mg groups and 0.4% for the placebo groups. In addition, a weight loss of 1.2 kg was achieved in the 3 mg group, with over 80% of subjects losing some weight versus a 0.4 kg reduction in the placebo group. In the first trial, weight losses of 2.0 kg and 1.3 kg, respectively, were observed in the 1.5 mg and 2.0 mg dose groups. PC-DAC-Exendin-4 was well tolerated.
October 27, 2008
Novo Nordisk issued positive results from a phase IIIb trial of liraglutide for the treatment of type II diabetes. This open-label, parallel, randomized study, dubbed LEAD-6, enrolled 464 type II diabetics receiving stable oral anti-diabetic therapy, in the US and Europe. The subjects were randomized to receive subcutaneous liraglutide 1.8 mg once daily or exenatide 10 micrograms twice daily for 26 weeks. The primary endpoint was HbA1c level at week 26. Liraglutide was significantly more effective at improving blood glucose control as measured by HbA1c, than exenatide. The percent change in HbA1C from baseline was -1.12 for the liraglutide group compared to -0.79 for the exenatide group (p<0.05). Fasting plasma glucose was also reduced significantly more with liraglutide compared to exenatide (-1.61 versus -0.60; p<0.05). In addition, liraglutide was also associated with higher HOMA-B values, an assessment of beta-cell function, with a 32.1% change from baseline compared to a 2.7 % change for the exenatide group (p<0.05). Liraglutide was well tolerated and the overall rate of hypoglycaemia was low. Regulatory submissions are currently under review by the FDA and EMEA.
September 15, 2008
Novo Nordisk released positive results from a phase III trial of liraglutide for the treatment of type II diabetes. This 26-week randomized trial, dubbed LEAD-4 (Liraglutide Effect and Action in Diabetes), enrolled 533 subjects. The subjects received once daily doses of liraglutide (1.2 mg or 1.8 mg) or placebo, all added to metformin 2 g (1 g, twice daily) and rosiglitazone 8 mg (4 mg, twice daily). The primary endpoint was the reduction in blood glucose levels (HbA1c) from baseline. Additional endpoints included decrease in fasting blood glucose levels, weight loss, blood pressure reduction and improvements in beta-cell functioning. The subjects in the liraglutide combination arm had a mean reduction of 1.5% from baseline HbA1c. More than half of these subjects reached the American Diabetes Association HbA1c target of <7.0% compared to 28% of those who received placebo (p<0.05). Fasting blood glucose levels decreased by -2.2 mmol/L and -2.4 mmol/L within two weeks on 1.2 and 1.8 mg of liraglutide, respectively (p<0.05). Treatment with both doses of liraglutide also led to significant loss in mean body weight of -1.02 kg and -2.02 kg, respectively, compared to an increase in weight of 0.6 kg in the metformin and rosiglitazone only group. Significant reductions in blood pressure were also observed, with reductions of 6.71 mmHg and 5.65 mmHg with liraglutide 1.2 mg and 1.8 mg, respectively, compared to a decrease of 1.11 mmHg in the comparator group (p<0.05). In addition, beta-cell function was also significantly improved over placebo. An MAA and NDA are currently under review by the FDA.
September 1, 2008
ActivX Biosciences Biosciences issued positive results from a phase IIa trial of KRP-104 for the treatment of type II diabetes. This randomized, double-blind, placebo-controlled study enrolled 220 subjects with type 2 diabetes inadequately controlled on metformin alone, in the US and India. The subjects received 120 mg of KRP-104, administered either as a once daily (QD) dose or as a split dose of 60 mg (BID) added to stable metformin therapy for 12-weeks of treatment. The primary endpoints of the study were reached. Both dosing regimens provided greater than 95% inhibition of dipeptidyl peptidase-4 (DPP-4) during daytime hours. However, the BID dosing regimen provided this level of inhibition continuously, whereas the QD dose resulted in considerably less DPP-4 inhibition overnight. Both KRP-104 dose groups demonstrated comparable, highly significant reductions in HbA1c of -0.64% (p < 0.0001) and -0.54% (p = 0.0003) in the 60 mg BID and 120 mg QD groups, respectively, compared with placebo over the 12-week treatment period. A key secondary endpoint was reached as well. KRP-104 significantly reduced fasting plasma glucose in the 60 mg BID and 120mg QD dose group compared with placebo. The safety and tolerability of KRP-104 were not substantially different from placebo. Based on the results, ActivX plans to continue with the development of KRP-104
July 14, 2008
Andromeda issued positive interim results from a phase III trial of DiaPep277 for the treatment of type I diabetes. This multinational, randomized, double-blind, placebo-controlled, parallel-group study enrolled 400 subjects with newly diagnosed type 1 diabetes. The subjects received DiaPep277 (1.0 mg plus 40 mg mannitol) or placebo in a 0.5ml lipid emulsion, administered subcutaneously on Days 0, 1, 3, 6, 9, 12, 15, 18 and 21 months. The primary endpoint was change from baseline in C-peptide AUC measured in a two hour mixed-meal tolerance test (MMTT). Reported data is from 137 subjects who had completed at least 12 months of therapy. The results showed that no significant drug related adverse events, serious adverse events or lab abnormalities. The effect of the drug was similar to that seen in previous studies. Based on the results, this trial will proceed as planned.
July 7, 2008
Vivus reported additional positive results from a phase III trial of Qnexa for the treatment of type II diabetes. Data are from a subset of subjects with higher cardiovascular risk factors at baseline. This randomized, double-blind, placebo-controlled study, dubbed OB-202, enrolled 206 subjects who underwent a four-week dose escalation period followed by 24 weeks of treatment. Following enrollment, subjects were stratified at randomization for either low HbA1c (7.0-8.0 percent) or high HbA1c (>8.0-12.0 percent). The subjects received Qnexa (15 mg phentermine/100 mg topiramate) or placebo. The primary endpoint was change in glycemic control as reflected by measurements of HbA1c. Secondary endpoints included weight loss and various cardiovascular risk factors. In the Qnexa arm systolic blood pressure was reduced by 11.2 mm Hg from a baseline mean of 138.1 mm Hg, as compared to a reduction of 1.9 mm Hg from a baseline mean of 140.7 mm Hg in the placebo group (p=0.006). Diastolic blood pressure was reduced by 7.9 mm Hg from a baseline mean of 83.5 mm Hg in the Qnexa group, as compared to a reduction of 3.3 mm Hg from a baseline mean of 86.3 mm Hg in the placebo group (p=0.015). Elevated triglyceride levels were also reduced by 86.9 mg/dL (32%) from baseline as compare to a reduction of 25.3 mg/dL (8.7%) in the placebo group (p=0.022). In addition, fasting plasma glucose in this higher-risk population was reduced by 85.2 mg/dL or 35% from a baseline mean of 245 mg/dL in the Qnexa group as compared to a reduction of 42.2 mg/dL or 17% from a baseline mean of 242.4 mg/dL in the placebo group (p=0.006). Additional studies of Qnexa are currently underway.
June 16, 2008
Bristol-Myers Squibb and AstraZeneca reported positive results from a phase III trial of saxagliptin for the treatment of type II diabetes. This multicenter, randomized, double-blind, placebo-controlled, parallel-group study enrolled 401 treatment nave subjects. The subjects were randomized to one of four separate treatment arms: saxagliptin 2.5 mg, 5 mg or 10 mg or placebo, once daily. The primary endpoint was the change from baseline to Week 24 in glycosylated hemoglobin level (A1C). The secondary endpoints of the study included achievement of A1C of less than 7 percent and changes from baseline in fasting plasma glucose (FPG). Saxagliptin 2.5 mg, 5 mg and 10 mg demonstrated a significant mean change in A1C from baseline of -0.4%, -0.5% and -0.5%, respectively, resulting in a placebo-adjusted change of -0.6%, -0.6% and -0.7%, respectively (p-value less than 0.0001). Reductions in A1C levels were seen as early as four weeks after initiation of saxagliptin treatment, the first scheduled A1C measurement point. A1C of less than 7 percent at Week 24 was observed in 35%, 38% and 41% of subjects in the saxagliptin 2.5 mg, 5 mg and 10 mg arms, respectively, compared to 24% of individuals treated with placebo (p-value not significant at the 2.5 mg dose; p-value at the other doses less than 0.05). Treatment was well tolerated; over 24 weeks saxagliptin had an adverse event profile similar to placebo. Saxagliptin was not associated with weight gain in any of the treatment groups. Based on positive phase III results Bristol-Myers Squibb and AstraZeneca plan to submit an NDA in the United States in mid 2008.
Novo Nordisk issued positive results from a phase III trial of liraglutide for the treatment of type II diabetes. This double-blinded, double-dummy, randomized, parallel group, actively-controlled, trial was dubbed LEAD 3 (Liraglutide Effect and Action in Diabetes) and enrolled 746 subjects internationally. The subjects received liraglutide (1.2 and 1.8 mg once daily) or glimepiride (8 mg once daily) for 52 weeks. All the subjects had been previously treated with diet/exercise or not more than half the maximum dose of one oral anti-diabetic drug for greater than or equal to two months. The primary endpoint was a change in HbA1c after 52 weeks. Both doses of liraglutide provided substantial improvement in glucose control from baseline and statistically significantly better glucose control than glimepiride. The mean HbA1c percent changes from baseline were -1.14, -0.84 and -0.51 and the percentage of subjects achieving HbA1C of <7% was 58.2%, 53.5% and 33.3% in the liraglutide 1.2 mg, 1.8 mg and glimepiride arms, respectively. In addition, there was significant mean weight loss in both liraglutide arms as compared to weight gain in the glimepiride arm (-2.45 kg and -2.05 kg versus 1.12 kg, respectively). Treatment was safe and well tolerated, with no major hypoglycaemic episodes reported. An NDA and MAA are currently under review by the FDA and EMEA.
May 5, 2008
Metabasis issued positive preliminary results from a phase IIa trial of MB07803 for the treatment of type II diabetes. This randomized, double-blind, placebo-controlled trial enrolled 105 subjects with a mean baseline fasting plasma glucose of 187 mg/dL and mean baseline HbA1c of 8.2%. The subjects received either placebo or MB07803 at an oral dose of 10, 50, 100 or 200 mg once daily for twenty eight days. The primary efficacy endpoint was change in fasting plasma glucose (FPG) at day twenty eight from baseline. This endpoint was achieved in the 200 mg dose group with statistically significant reduction in FPG versus placebo (p=0.0177). Treatment was safe and well tolerated in all dose groups, with an adverse event profile similar to that of the placebo. Fasting lactate levels were within the normal range and no subjects experienced hyperlacticemia. Metabasis plans to report full results later in 2008.
April 21, 2008
AtheroGenics reported positive interim results from an ongoing phase III trial of AGI-1067 for the treatment of type II diabetes. This double-blind, placebo controlled, six-month trial, dubbed ANDES (AGI-1067 as a Novel Anti-Diabetic Agent Evaluation Study), enrolled nine hundred and ninety nine subjects. The subjects received one of two doses of AGI-1067 (75 mg or150 mg) or placebo. The primary endpoint was an improvement in hemoglobin A1c at six months when compared to baseline. The interim analysis of eight hundred and six subjects who completed three months in the study showed dose-related, statistically significant reductions in A1c. The mean changes for subjects in the 150 mg, 75 mg, and placebo arms were 0.5%, 0.3%, and 0.1%, respectively (p < 0.001 for 150 mg versus placebo, p=0.001 for 75 mg versus placebo). AGI-1067 was well-tolerated with no difference in discontinuations between the two treatment arms. Based on the results AtheroGenics plans to continue with the trial as planned.
Sirtris issued positive results from a phase Ib study of SRT501 for the treatment of type II diabetes. This multi-center, blinded and randomized trial enrolled one hundred subjects who received one of three oral dose regimens: 1.25 grams of SRT501 twice daily, 2.5 grams twice daily or placebo twice daily. The group who received SRT501 2.5 grams twice a day had significantly lower blood glucose levels compared to placebo. This was determined through an oral glucose tolerance test (OGTT) at the test's two-hour time point. This arm also showed a statistically significant lowering of both fasting blood glucose and glucose levels after meals (the postprandial period). A strong trend in lowering postprandial insulin levels was also observed. While not reaching statistical significance, SRT501 at 1.25 grams given twice per day lowered fasting and postprandial glucose, and glucose when challenged with an OGTT at the two-hour time point on day twenty seven of the trial as compared to the placebo group. SRT501 was found to be safe and well tolerated, with no evidence of drug accumulation. A phase II trial of SRT501 is currently underway.
February 18, 2008
Bentley issued positive preliminary results from a phase II trial of Nasulin for the treatment of type II diabetes. This open label, randomized, parallel group study enrolled eighty subjects in India. The trial was designed to compare Nasulin as add-on to oral anti-diabetic therapy or oral anti-diabetic therapy alone. The subjects self-administered Nasulin spray three times per day for twelve weeks. The primary endpoints were reduction of Post Prandial Blood Sugar (PPBS) by 20mg/dl from the baseline value and reduction of glycosylated hemoglobin (HbA1c) by 0.7% from the baseline value. Initial results revealed that the subjects receiving Nasulin reached their primary endpoint for PPBS after two months, with an average decline of 49mg/dl. However, PPBS values increased in month three, apparently to levels above the primary endpoint. HbA1c levels also declined by an average of 0.7 or more after two months. However, HbA1c levels also increased in month three, again to levels above the primary endpoint. Nasulin was well tolerated, with no reported serious adverse events, no overall weight gain over the three month interval and no indication of severe hypoglycemia. Based on the results, Bentley plans to move forward with the development of Nasulin.
Depomed released positive results from a phase II trial of Gabapentin GR for the treatment of menopausal hot flashes. This thirteen week, double-blind, placebo-controlled, multi-center trial enrolled one hundred and twenty four menopausal women with recurrent, moderate to severe hot flashes, in the United States. The subjects were placed into three active treatment arms: each arm remained on a stable Gabapentin GR dose for five weeks at an initial dose (600mg once daily; 1200mg in divided 600mg doses; or 1200mg once daily), followed by five weeks on a stable, incrementally higher dose (1800mg in divided 600mg and 1200mg doses; 2400mg in divided 600 and 1800mg doses; and 3000mg in divided 1200mg and 1800mg doses). Each stable dosing regimen was preceded by a one-week titration period. The primary endpoint was a reduction in the frequency and severity of hot flashes compared to baseline. Data revealed statistically significant results over placebo from baseline to the end of the study in the 1800mg and 2400mg treatment groups. In the 1800mg treatment group, the mean number of moderate to severe hot flashes was reduced from 10.1 at baseline to 2.7 at endpoint (p=0.016), with similar results in the 2400mg treatment groups, compared to an endpoint value of 5.1 for the placebo group. Treatment was well tolerated. Based on the results, Depomed plans to move forward with phase III development.
December 10, 2007
Amylin and Eli Lilly reported positive results from a trial of Byetta monotherapy for the treatment of type II diabetes. This twenty four-week randomized, placebo-controlled study enrolled two hundred and thirty two drug-nave subjects who received subcutaneous injections of placebo, 5 mcg Byetta or 10 mcg Byetta twice daily without taking any oral antidiabetes agents. The subjects randomized to 10 mcg exenatide received 5 mcg injections for the first 4 weeks, and increased to 10 mcg injections for the final 20 weeks. significant reductions in A1C (a measure of average blood sugar over 3 months) were observed in both the 5 mcg and 10 mcg Byetta treatment arms, with a decrease of 0.7 percentage points and 0.9 percentage points, respectively, from an average baseline A1C ranging from 7.8 to 7.9 percent. In addition, at the conclusion of the study approximately 60% of the subjects in both Byetta had an A1C of 7 percent or less, a target level for glucose control. Based on the results Amylin and Eli Lilly plan to file for the US regulatory approval of Byetta monotherapy in the first half of 2008.
October 15, 2007
DiaMedica announced positive results from a phase II trial of DM-71 for the treatment of type II diabetes. This single dose, single blinded, placebo controlled, 12 week trial enrolled 64 subjects in Canada. The subjects received DM-71 three times daily, one hour before each meal, along with their current therapy. All primary endpoint were met. In the evaluable population, DM-71 had an absolute reduction of 0.32% from baseline of mean HbA1c (p=0.0066), compared to the placebo group with a non-clinically significant reduction from baseline (0.22%, p=0.1027). In a pre-specified sub-group of subjects with moderate and higher elevated HbA1c (greater than or equal to 8.0%), DM-71 had an absolute reduction of 0.55% from baseline of mean HbA1c (p=0.0063). The placebo group was not statistically different than baseline (increase 0.03%, p=0.9750). A key secondary endpoint was achieved as well. DM-71 was shown to have a statistically significant absolute weight reduction of 1.38 kg from baseline of mean weight per patient (p=0.0005). Based on the results, DiaMedica plans to move forward with the development of DM-71.
October 1, 2007
Novo Nordisk issued positive data from a phase III trial of liraglutide for the treatment of type 2 diabetes. This 26-week, randomized, controlled, double-blind trial, dubbed LEAD-4 (Liraglutide Effect and Action in Diabetes), enrolled 533 subjects. Following a run-in period with metformin and rosiglitazone, the subjects received add-on treatment with either liraglutide or placebo. The average baseline HbA1c level was 8.5% and the average body weight was just above 95 kg. At the end of the study, more than 50% of the subjects in the liraglutide arm reached the goal of HbA1c < 7% and more than 35% reached an HbA1c of = 6.5%. In addition, liraglutide reduced body weight by 2.5 kg compared to placebo. A final phase III trial of liraglutide is currently underway.
August 27, 2007
Novo Nordisk reported positive results from two phase III trials of liraglutide for the treatment of type II diabetes. Both 26-week studies are part of the LEAD (Liraglutide Effect and Action in Diabetes) program. The trials comprised a total of 2,132 subjects whose diabetes was inadequately controlled by one or two oral anti-diabetic drugs. Following a run-in period to determine a maximum tolerated dose of glimepiride, subjects in LEAD 1 were randomized to receive placebo, rosiglitazone or liraglutide. Approximately 40% of the subjects treated with liraglutide reached HbA1c below 7%. This goal was also reached by 50% of liraglutide-treated subjects who had previously received a single oral antidiabetic drug, for a total HbA1c reduction of approximately 1 to 1.5%. Following a run-in period to determine the maximum tolerated dose of metformin, subjects in LEAD 2 were randomized to treatment with placebo, glimepiride or liraglutide. More than 40% of subjects achieved the HbA1c target of 7%. Among those previously treated with a single oral antidiabetic drug, close to 65% reached the target. In addition, a weight difference of between 2 and 4 kg in favor of liraglutide was found when compared to rosiglitazone and glimepiride treatment, respectively. Results from the remaining LEAD trials are expected by the end of 2007 and beginning of 2008, with regulatory filing anticipated by mid-2008.
July 23, 2007
Metabasis and Daiichi Sankyo issued negative results from a phase IIb trial of CS-917 for the treatment of type II diabetes. This multi-center, double-blind, placebo-controlled trial enrolled 392 subjects who were divided into four treatment arms to receive CS-917 at 50 mg BID or 100 mg BID, metformin at 850 mg BID or placebo, for three months. Both doses of CS-917 failed to meet the primary endpoint of significantly lowering the placebo-adjusted level of glycosylated hemoglobin (HbA1c), a measure of glucose load. The mean HbA1c level at the start of the study was approximately 7.6-7.7%. The placebo adjusted HbA1c level at the end of treatment was unchanged at the CS-917 low dose and there was a 0.17% decrease at the high dose (p=0.1256). Metformin treatment resulted in a placebo-adjusted decrease of HbA1c of 0.50% (p less than 0.0001). Metabasis and Daiichi Sankyo plan to fully evaluate the data to determine a future course of action.
July 2, 2007
Bristol-Myers Squibb and AstraZeneca reported positive results from a phase III trial of saxagliptin for the treatment of type II diabetes. This trial enrolled 743 subjects with type II diabetes on a stable dose of metformin (1500 to 2550 mg/day). Subjects were randomized to receive add-on saxagliptin 2.5 mg, 5 mg, 10 mg, or placebo once daily. The primary endpoint was the change from baseline in hemoglobin A1C levels through 24 weeks. At the end of24 weeks, subjects receiving saxagliptin+metformin demonstrated statistically significant decreases in hemoglobin A1C levels compared to placebo+metformin: -0.73%, -0.83% and -0.72% at the 2.5 mg, 5 mg and 10 mg doses, respectively (p less than 0.0001). The secondary endpoints were achieved as well. Reduction in fasting plasma glucose was reached with subjects in the saxagliptin+metformin arm showing a decrease of -16 mg/dL, -23 mg/dL, and -22 mg/dL for saxagliptin 2.5 mg, 5 mg and 10 mg, respectively, compared to placebo + metformin (p less than 0.0001). In addition, the percentage of subjects with hemoglobin A1C less than 7 percent at week 24 was 17% for placebo+metformin compared to 37%, 44% and 44% for the 2.5 mg, 5 mg and 10 mg doses of saxagliptin respectively (p less than 0.0001). Investigator-reported hypoglycemia, with or without confirmation, were reported in 9 subjects on placebo+metformin, and 15, 10 and 7 subjects, on 2.5 mg, 5 mg, and 10 mg saxagliptin+metformin, respectively. Based on the results, the companies plan to move forward with the development of saxagliptin.
June 25, 2007
Novo Nordisk issued positive results from a phase III trial of liraglutide for the treatment of type II diabetes. This randomized, controlled, double-blind trial, dubbed LEAD ((Liraglutide Effect and Action in Diabetes), enrolled 581 subjects with inadequately controlled type II diabetes, internationally. Subjects received metformin and a sulfonylurea, two widely used diabetic therapies, along with one daily injection of liraglutide, placebo or insulin glargine. At baseline, the average HbA1c level was between 8.0% and 8.5%. At the end of the study, more than 50% of subjects in the liraglutide group had reached the American Diabetes Association goal of HbA1c < 7%. In addition, 35% achieved the American Association of Clinical Endocrinologists HbA1c target of <= 6.5%, a statistically significant difference when compared to the insulin glargine group (p=0.2). Statistical significance was also reached in the difference in body weight between the liraglutide and insulin glargine treatment groups at the end of the study, with an average 3.5 kg difference. Four additional phase III trials of liraglutide are currently underway. Novo Nordisk plans to announce results from these trials during the second half of 2007 and the first half of 2008.
June 23, 2003
Amylin Pharmaceuticals reported encouraging results from a phase III trial investigating exenatide (synthetic exendin-4), a glucagon-like peptide agonist for the treatment of type 2 diabetes. Result showed that most subjects who completed 20 weeks of treatment achieved average glucose levels within the American Diabetes Association's (ADA) target range. In addition, exenatide decreased both fasting and post-prandial glucose levels. The most frequently reported adverse event was mild to moderate nausea and hypoglycemia. The overall dropout rate was approximately 18%, with nausea being responsible for 8%. The open-label study enrolled 77 subjects who have been using exenatide for 20 weeks. Results were presented at the ADA's 63rd Scientific Sessions in New Orleans, Louisiana.
September 3, 2002
Roche's four-year landmark study of Xenical, an FDA-approved weight-loss medication, demonstrated that the drug can prevent or delay the development of type 2 diabetes. The study, which involved 3,304 subjects, compared the effects of Xenical plus lifestyle intervention to lifestyle intervention alone. Results showed that the risk of developing type 2 diabetes was 37% lower in subjects treated with Xenical plus lifestyle intervention. In addition, weight loss was significantly greater and successfully maintained in nearly twice as many subjects in the Xenical treated group. Cardiological risk factors were also significantly improved with Xenical plus lifestyle intervention. Roche is looking to add the type 2 diabetes indication to its Xenical prescription label.
January 21, 2002
Phase II trial results suggest that a single daily dose of Insmed's SomatoKine is an effective adjunct to insulin in type 2 diabetic subjects whose blood glucose is poorly controlled by standard insulin regimens. In the placebo-controlled and double-blinded trial, 37 subjects were randomized to receive either placebo or SomatoKine at dose levels between 0.125-2.0 mg/kg once daily in the evening. All subjects continued to receive appropriate insulin doses during the treatment period. At a dose of 2.0 mg/kg, a significant decrease in average daily insulin requirement from 70.8 units at baseline to 56.5 units at the end of the treatment period was observed. Additionally, fasting blood glucose decreased from 171.5 mg/dl to 102.2 mg/dl in subjects receiving 2.0 mg/kg of SomatoKine, versus a decrease from 151.5 mg/dl to 134.8 mg/dl for placebo-treated subjects.