HARMONY 3: 104-week trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride

Ahrén B, Johnson SL, Stewart M, et al; for the HARMONY 3 Study Group. HARMONY 3: 104-week randomized, double-blind, placebo- and active-controlled trial assessing the efficacy and safety of albiglutide compared with placebo, sitagliptin, and glimepiride in patients with type 2 diabetes taking metformin. Diabetes Care. 2014;37(8):2141-2148.

In the HARMONY 3 study, albiglutide demonstrated significant A1C and FPG reductions compared with sitagliptin, glimepiride, and placebo in patients with type 2 diabetes inadequately controlled with metformin.

A1C
Percent A1C change from baseline to Week 104:

  • Albiglutide 30 mg QW* + metformin (n=302): -0.63%
  • Sitagliptin 100 mg QD + metformin (n=302): -0.28%; vs albiglutide: -0.4% (95% CI, -0.5 to -0.2); P=0.0001
  • Glimepiride 2 mg QD + metformin (n=307): -0.36%; vs albiglutide: -0.3% (95% CI, -0.5 to -0.1); P=0.0033
  • Placebo + metformin (n=101): +0.27%; vs albiglutide: -0.9% (95% CI, -1.2 to -0.7); P<0.0001

More subjects who received albiglutide reached A1C <6.5%, <7.0%, and <7.5% vs comparators at Week 104. Albiglutide had a more durable A1C effect vs comparators: mean A1C 7.5% with albiglutide at Week 104 vs 7.8% with sitagliptin, 7.8% with glimepiride, and 8.4% with placebo. Baseline A1C was 8.1%-8.2% across groups.

Click on slide thumbnail to view larger. Slide available for download in the slide library.
HARMONY 3: Significant A1C Reductions With Albiglutide Vs Sitagliptin, Glimepiride, and Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Metformin   
HARMONY 3: Significant A1C Reductions With Albiglutide
Vs Sitagliptin, Glimepiride, and Placebo in Patients
With Type 2 Diabetes Inadequately Controlled With Metformin
 


FPG
Significant FPG reductions were seen with albiglutide vs sitagliptin, glimepiride, and placebo. FPG at Week 104:

  • Albiglutide 30 mg QW* + metformin (n=296): 147 mg/dL (8.2 mmol/L)
  • Sitagliptin 100 mg QD + metformin (n=299): 163 mg/dL (9.1 mmol/L); albiglutide was statistically superior to sitagliptin: -16 mg/dL (-0.9 mmol/L); P=0.0002
  • Glimepiride 2 mg QD + metformin (n=302): 159 mg/dL (8.8 mmol/L); albiglutide was statistically superior to glimepiride: -10 mg/dL (-0.6 mmol/L); P=0.0133
  • Placebo + metformin (n=100): 174 mg/dL (9.7 mmol/L); albiglutide was statistically superior to placebo: -28 mg/dL (-1.5 mmol/L); P<0.0001

Baseline FPG was 162.8-167.4 mg/dL (9.0-9.3 mmol/L) across groups.

Click on slide thumbnail to view larger. Slide available for download in the slide library.
HARMONY 3: Significant FPG Reductions With Albiglutide Vs Sitagliptin, Glimepiride, and Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Metformin   
HARMONY 3: Significant FPG Reductions
With Albiglutide Vs Sitagliptin, Glimepiride,
and Placebo in Patients With Type 2 Diabetes
Inadequately Controlled With Metformin
 


Weight loss
Weight loss from baseline to Week 104, kg:

  • Albiglutide 30 mg QW* + metformin (n=296): -1.21 kg
  • Sitagliptin 100 mg QD + metformin (n=300): -0.86 kg
  • Glimepiride 2 mg QD + metformin (n=302): +1.17 kg; significant difference vs albiglutide (P<0.0001)
  • Placebo + metformin (n=100): -1.0 kg

Baseline weight was 89.6-91.8 kg across groups.

Click on slide thumbnail to view larger. Slide available for download in the slide library.
HARMONY 3 Weight Loss With Albiglutide Vs Sitagliptin Glimepiride and Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Metformin   
HARMONY 3: Weight Loss With
Albiglutide Vs Sitagliptin, Glimepiride,
and Placebo in Patients With Type 2 Diabetes
Inadequately Controlled With Metformin
  


Hyperglycemic rescue
Fewer albiglutide-treated patients compared with those assigned to sitagliptin, glimepiride, or placebo, received hyperglycemic rescue in the HARMONY 3 study. Percentage of patients receiving hyperglycemic rescue:

  • Albiglutide 30 mg QW* + metformin (n=297): 25.8%
  • Sitagliptin 100 mg QD + metformin (n=300): 36.4%; difference between baseline and time to rescue: P=0.0118
  • Glimepiride 2 mg QD + metformin (n=302): 32.7%
  • Placebo + metformin (n=100): 59.2%; difference between baseline and time to rescue: P<0.00001

Click on slide thumbnail to view larger. Slide available for download in the slide library.
HARMONY 3: Fewer Albiglutide-Treated Patients Received Hyperglycemic Rescue Vs Sitagliptin, Glimepiride, and Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Metformin   
HARMONY 3: Fewer Albiglutide-Treated
Patients Received Hyperglycemic Rescue
Vs Sitagliptin, Glimepiride, and Placebo
in Patients With Type 2 Diabetes Inadequately
Controlled With Metformin
  


Safety and adverse events
Regarding AEs to Week 104 in the HARMONY 3 study:

  • Percentage of patients with any AEs relatively balanced across groups: albiglutide 83.8%, sitagliptin 79.1%, glimepiride 83.1%, placebo 79.2%
  • Most frequent in patients taking albiglutide (>7% of patients): upper respiratory tract infection, diarrhea, nausea, injection-site reaction, hypertension, nasopharyngitis, cough
  • Percentage of patients with serious AEs similar with albiglutide (12.9%) vs sitagliptin (9.9%) and glimepiride (11.7%); fewer serious AEs with albiglutide vs placebo (15.8%)
  • GI AEs similar between albiglutide and placebo; fewer with sitagliptin and glimepiride
  • Documented symptomatic hypoglycemia (70 mg/dL [≤3.9 mmol/L]) prior to rescue was similar with albiglutide (3.0%) vs placebo (4.0%) and sitagliptin (1.7%) vs glimepiride (17.9%)
  • Two probable pancreatitis events possibly related to albiglutide 

All subjects were receiving metformin + study medication.

 Click on slide thumbnail to view larger. Slide available for download in the slide library.
HARMONY 3: Safety and AEs With Albiglutide Vs Sitagliptin, Glimepiride, and Placebo in Patients With Type 2 Diabetes Inadequately Controlled With Metformin   
HARMONY 3: Safety and AEs With Albiglutide
Vs Sitagliptin, Glimepiride, and Placebo
in Patients With Type 2 Diabetes
Inadequately Controlled With Metformin
 

About this study
The HARMONY 3 study assessed the efficacy and safety of the GLP-1 receptor agonist, albiglutide, vs sitagliptin, glimepiride, and placebo. Subjects had type 2 diabetes inadequately controlled with metformin, A1C 7%-10%, and body mass index 20-45 kg/m2. Randomization was 3:3:3:1 (metformin continued) to: albiglutide 30 mg QW* (n=302), sitagliptin 100 mg QD (n=302), glimepiride 2 mg QD (n=307), or placebos matched to albiglutide, sitagliptin, glimepiride (n=101). The primary endpoint was percent A1C change from baseline to Week 104. Secondary endpoints included achievement of A1C targets, FPG change, and weight change.

None of the agents discussed is FDA approved for weight loss. 

*Titrated to 50 mg if persistent hyperglycemia; mean dose at Week 104: 40.5 mg
Titrated to 4 mg if persistent hyperglycemia; mean dose at Week 104: 3.1 mg

AE=adverse event; BMI=body mass index; GI=gastrointestinal; QD=once daily; QW=once weekly

Related content: 

Conference coverage: Novel GLP-1 Receptor Agonists Show Promise for Glycemic Control (login required) 

  

Any pharmacologic agents discussed are approved for use in the United States by the U.S. Food and Drug Administration (FDA) unless otherwise noted. Consult individual prescribing information for approved uses outside of the United States. 

September 2014 

This overview was created by KnowledgePoint360 Group, LLC, and was not associated with funding via an educational grant or a promotional/commercial interest.  

Previous Article
Metformin does not affect cancer risk: a cohort study in the U.K. Clinical Practice Research Datalink analyzed like an intention-to-treat trial
Next Article
Higher potency statins and the risk of new diabetes: multicentre, observational study of administrative databases 

Back to
Recent Diabetes Articles 

BG Footer

 

 

Last Modified: 9/19/2014