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, Aug 2014

OBJECTIVE To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

https://care.diabetesjournals.org/content/37/8/2141.full.pdf

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

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 C L I N C A R E / E D U C A T I O N / N U T R II T O N / P S Y C H O S O C I A L 0 Deborah T. Cirkel 1 Murray Stewart 2 Susan L. Johnson 3 for the HARMONY 3 Study Group 4 and Mark N. Feinglos RESEARCH DESIGN AND METHODS Patients with type 2 diabetes receiving metformin were randomized to albiglutide (30 mg), sitagliptin (100 mg), glimepiride (2 mg), or placebo. Blinded dose titration for albiglutide (to 50 mg) and glimepiride (to 4 mg) was based on predefined hyperglycemia criteria. The primary end point was change in HbA1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue. OBJECTIVE To compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo. RESULTS Baseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA1c was 8.1% (65.0 mmol/mol); mean age was 54.5 years. The mean doses for albiglutide and glimepiride at week 104 were 40.5 and 3.1 mg, respectively. At week 104, albiglutide significantly reduced HbA1c compared with placebo (20.9% [29.8 mmol/mol]; P < 0.0001), sitagliptin (20.4% [24.4 mmol/mol]; P = 0.0001), and glimepiride (20.3% [23.3 mmol/mol]; P = 0.0033). Outcomes for FPG and HbA1c were similar. Weight change from baseline for each were as follows: albiglutide 21.21 kg (95% CI 21.68 to 20.74), placebo 21.00 kg (95% CI 21.81 to 20.20), sitagliptin 20.86 kg (95% CI 21.32 to 20.39), glimepiride 1.17 kg (95% CI 0.70–1.63). The difference between albiglutide and glimepiride was statistically significant (P < 0.0001). Hyperglycemic rescue rate at week 104 was 25.8% for albiglutide compared with 59.2% (P < 0.0001), 36.4% (P = 0.0118), and 32.7% (P = 0.1504) for placebo, sitagliptin, and glimepiride, respectively. Rates of serious adverse events in the albiglutide group were similar to comparison groups. Diarrhea (albiglutide 12.9%, other groups 8.6–10.9%) and nausea (albiglutide 10.3%, other groups 6.2–10.9%) were generally the most frequently reported gastrointestinal events. CONCLUSIONS Added to metformin, albiglutide was well tolerated; produced superior reductions in HbA1c and FPG at week 104 compared with placebo, sitagliptin, and glimepiride; and resulted in weight loss compared with glimepiride. The management of type 2 diabetes has become an increasingly complex practice given the number of treatments available (1). Despite the availability of new therapeutic agents, many patients with type 2 diabetes continue to have uncontrolled glycemia (2–4), and treatment adherence varies but remains relatively poor (5–9). Among patients taking metformin but who do not have adequately controlled diabetes, data are limited regarding next-step concomitant treatment (10). As a result, extended head-to-head comparisons of type 2 diabetes medications mirroring treatment algorithms (i.e., combinations with metformin) are needed to aid clinicians in making treatment decisions (11,12). Recent treatment guidelines have positioned incretin-based therapies, such as GLP-1 receptor agonists (GLP-1RAs), as alternative first-line therapies in certain clinical settings and as second-line therapies following metformin because of their substantial effectiveness in improving glycemic control as well as other positive effects, such as weight loss and low hypoglycemia rates (10,13,14). Albiglutide is a novel, once-weekly, long-acting GLP-1RA composed of a dipeptidyl peptidase-4 (DPP-4)2resistant GLP-1 dimer fused to recombinant human albumin. This structure affords an extended half-life of ;5 days and, as a consequence, once-weekly dosing (15,16). In a multinational phase 2b study of type 2 diabetes, albiglutide 30 mg once-weekly reduced HbA1c by 20.87% (29.5 mmol/mol) and also reduced fasting plasma glucose (FPG) and weight, with a low incidence of gastrointestinal (GI) adverse events (AEs) (16). The HARMONY program for albiglutide includes eight pivotal phase 3 studies designed to evaluate the efficacy and safety of albiglutide compared with placebo, oral antidiabetes medications, insulin glargine, and another GLP-1RA in a typical type 2 diabetic population (17,18). Here, we present 2-year primary end point data for HARMONY 3, which is a 3-year phase 3 study comparing the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo in patients with diabetes receiving metformin but not adequately controlled by the medication. Study Design This was a phase 3, randomized, doubleblind, placebo- and active-controlled parallel-group study that occurred between 17 February 2009 and 21 March 2013; the study comprised 4 study period (...truncated)


This is a preview of a remote PDF: https://care.diabetesjournals.org/content/37/8/2141.full.pdf

Bo Ahrén, Susan L. Johnson, Murray Stewart, Deborah T. Cirkel, Fred Yang, Caroline Perry, Mark N. Feinglos. 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, pp. 2141-2148, 37/8, DOI: 10.2337/dc14-0024