Molly C. Carr

Efficacy and tolerability of albiglutide versus placebo or pioglitazone over 1 year in people with type 2 diabetes currently taking metformin and glimepiride: HARMONY 5

To investigate the efficacy and tolerability of albiglutide, a weekly glucagon‐like peptide‐1 receptor agonist, when added to metformin and glimepiride in a triple therapy regimen in people with type 2 diabetes mellitus.

Efficacy and Safety of the Once-Weekly GLP-1 Receptor Agonist Albiglutide Versus Sitagliptin in Patients With Type 2 Diabetes and Renal Impairment: A Randomized Phase III Study

OBJECTIVE To evaluate weekly subcutaneous albiglutide versus daily sitagliptin in renally impaired patients with type 2 diabetes and inadequately controlled glycemia on a regimen of diet and exercise and/or oral antihyperglycemic medications. RESEARCH DESIGN AND METHODS In this phase III, randomized, double-blind, multicenter, 52-week study, the primary study end point was HbA1c change from baseline at week 26 in patients with renal impairment, as assessed with estimated glomerular filtration rate and categorized as mild, moderate, or severe (≥60 to ≤89, ≥30 to ≤59, and ≥15 to ≤29 mL/min/1.73 m2, respectively). Secondary end points included fasting plasma glucose (FPG), weight, achievement of treatment targets, hyperglycemic rescue, and safety. RESULTS Baseline demographics were similar across treatment and renal impairment groups with overall mean age of 63.3 years, BMI of 30.4 kg/m2, HbA1c of 8.2% (66 mmol/mol), and diabetes disease duration of 11.2 years. HbA1c change from baseline at week 26 was significantly greater for albiglutide than sitagliptin (−0.83% vs. −0.52%, P = 0.0003). Decreases in HbA1c, FPG, and weight were seen through week 52. Time to hyperglycemic rescue through week 52 was significantly longer for albiglutide than sitagliptin (P = 0.0017). Results of safety assessments were similar between groups, and most adverse events (AEs) were mild or moderate. The incidences of gastrointestinal AEs for albiglutide and sitagliptin were as follows: overall, 31.7%, 25.2%; diarrhea, 10.0%, 6.5%; nausea, 4.8%, 3.3%; and vomiting, 1.6%, 1.2%, respectively. CONCLUSIONS Once-weekly albiglutide therapy in renally impaired patients with type 2 diabetes provided statistically superior glycemic improvement with almost similar tolerability compared with daily sitagliptin therapy.

Albiglutide does not impair the counter-regulatory hormone response to hypoglycaemia: a randomized, double-blind, placebo-controlled, stepped glucose clamp study in subjects with type 2 diabetes mellitus†

To determine if the glucagon‐like peptide‐1 (GLP‐1) receptor agonist albiglutide, once weekly, impairs counter‐regulatory responses during hypoglycaemia.

Albiglutide for the treatment of type 2 diabetes mellitus : An integrated safety analysis of the HARMONY phase 3 trials

AIMS Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) stimulate the incretin system and lower glycaemic parameters in type 2 diabetes mellitus (T2DM). This analysis of clinical studies of up to 3years evaluated the safety of albiglutide, a GLP-1 RA, in people with T2DM. METHODS Integrated safety analysis included seven phase-3 T2DM studies of albiglutide compared with placebo and/or active comparators (a dipeptidyl peptidase-4 inhibitor, GLP-1 RA, insulin, sulphonylurea, and thiazolidinedione). RESULTS Studies of 32months (HARMONY 7), 1year (HARMONY 6), and 3years (HARMONY 1-5), reported similar rates of adverse events (AEs) (84.8%, 82.3%), and serious AEs (13.1%, 12.9%) between albiglutide and all comparators, respectively. AEs that did not differ between the groups included symptomatic or severe hypoglycaemia as well as nausea (12.0%, 11.3%) and vomiting (5.3%, 4.7%) for albiglutide and all comparators, respectively. According to the Medical Dictionary for Regulatory Activities preferred terms, only diarrhoea (13.7%, 9.9%), injection-site reaction (9.0%, 2.0%), and peripheral oedema (4.5%, 6.8%) had at least 2% difference between the albiglutide and all-comparator groups. In a similar integrated analysis, pancreatitis occurred more often with albiglutide (0.3%, 0.1%). Renal and cardiac function did not differ between the two groups. CONCLUSIONS In an integrated analysis of seven phase 3 clinical trials, albiglutide-treated patients experienced frequencies of AEs (including cardiovascular and renal) similar to the all-comparators group treated with other T2DM medications or placebo. Albiglutide treatment was associated with higher rates of diarrhoea and injection-site reactions, but not increased nausea and vomiting, versus all comparators.

Three-year data from 5 HARMONY phase 3 clinical trials of albiglutide in type 2 diabetes mellitus: Long-term efficacy with or without rescue therapy

AIMS Diabetes therapies that provide durable glycaemic control for people with type 2 diabetes mellitus (T2DM) are needed. We present efficacy results of albiglutide, a glucagon-like peptide-1 receptor agonist, in people with T2DM over a 3-year period. METHODS Five of the 8 HARMONY phase 3 trials, comparing albiglutide with other therapies or placebo across a spectrum of clinical care, lasted for a preplanned 3years. Participants with uncontrolled hyperglycaemia who met predetermined criteria could receive rescue medication. The ability to remain on study medication without needing additional rescue was an efficacy measure. Glycaemic measures and body weight were analysed in 2 populations: those who remained rescue-free and all participants. RESULTS Participants (n=3132) were randomised to albiglutide or comparator. A greater proportion of participants who received albiglutide remained rescue-free (55-71%) compared with placebo (35-51%; p<0.001 to p=0.002). The proportion of rescue-free participants with albiglutide did not differ from glimepiride or insulin glargine, was higher than with sitagliptin (p=0.013), and lower than with pioglitazone (p=0.045). At 3years, albiglutide was associated with clinically significant reductions in hyperglycaemia (eg, rescue-free participants: HbA1c -0.52% [SE0.11] to -0.98% [0.12]; -5.7mmol/mol [1.2] to -10.7mmol/mol [1.3] and all participants: HbA1c -0.29% [0.11] to-0.92% [0.13]; -3.2mmol/mol [1.2] to -10.1mmol/mol [1.4]). Albiglutide was also associated with modest reductions in body weight vs pioglitazone, glimepiride, and insulin glargine, which were associated with weight gain. CONCLUSION These 3-year efficacy data support long-term use of albiglutide in the management of people with T2DM. ClinicalTrials.gov NCT00849056, NCT00849017, NCT00838903, NCT00838916, NCT00839527.

Albiglutide, a weekly GLP-1 receptor agonist, improves glycemic parameters in Japanese patients with type 2 diabetes over 1 year when added to single oral antidiabetic drugs

Abstract Objective: To evaluate the safety and efficacy of once weekly albiglutide added to a single oral antidiabetic drug (OAD) in Japanese patients with inadequately controlled type 2 diabetes mellitus (T2DM). Research design and methods: In this phase 3, 1 year study (NCT01777282), patients (N = 374) received albiglutide 30 mg plus a single OAD (sulfonylurea [n = 120], biguanide [n = 67)], glinide [n = 65], thiazolidinedione [n = 61], or α-glucosidase inhibitor [n = 61]). Albiglutide could be increased to 50 mg after Week 4, based on glycemic criteria. Primary endpoints were the incidence of adverse events (AEs) and hypoglycemia; secondary endpoints were changes from baseline at Week 52 in HbA1c and fasting plasma glucose (FPG), proportion of patients achieving HbA1c ≤7.0%, and withdrawals due to hyperglycemia. Results: On-therapy AEs occurred in 78.6% of patients and serious AEs in 2.1%. Common AEs were nasopharyngitis (32.6%), constipation (7.2%), and diabetic retinopathy (5.3%). No serious AEs occurred more than once or were reported in >1 patient. Hypoglycemia occurred in 6.4% of patients, mostly in the albiglutide + sulfonylurea (14.2%) and the albiglutide + glinide (6.2%) groups. Albiglutide was uptitrated in 53.2% of patients. Mean baseline HbA1c was 8.1%. Mean decreases from baseline in HbA1c were observed with the addition of albiglutide to thiazolidinediones (−1.42%), α-glucosidase inhibitors (−1.39%), sulfonylureas (−1.04%), glinides (−0.95%), and biguanides (−0.94%). HbA1c of <7% in >50% of patients and mean reductions in FPG were achieved in all groups. Mean changes from baseline in body weight ranged from +0.52 kg (albiglutide + thiazolidinedione) to −0.33 kg (albiglutide + biguanide). Limitations of the study included open label treatment that was not randomized. Conclusions: When combined with a single OAD in Japanese patients with inadequately controlled T2DM, albiglutide led to favorable changes in all glycemic parameters, with minor changes in body weight depending on the background OAD. No new safety concerns were noted.

Postprandial plasma glucose effects of once-weekly albiglutide for the treatment of type 2 diabetes.

ABSTRACT Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) vary in their structure, duration of action, efficacy, and safety. In order to optimize glycemic control, it is important to target both fasting (FPG) and postprandial plasma (PPG) glucose. Although phase 3 trials document the effect of GLP-1 RAs on glycated hemoglobin, few data are available to assess their effect on PPG. Albiglutide is a once-weekly GLP-1 RA with a half-life of ≈ 5 days. The goal of this review is to summarize the effects of albiglutide on PPG in four phase 2 trials and to describe the PPG-lowering effects of the GLP-1 RAs. At clinically relevant doses (30-64 mg), albiglutide consistently lowered PPG after each meal in addition to its effect on lowering FPG. Multiple weekly subcutaneous injections of albiglutide led to improvements in a variety of glycemic measures, including maximal reductions in PPG from baseline, postmeal glucose excursions, and FPG. Albiglutide, a longer-acting GLP-1 RAs, provides reductions in FPG, PPG following meals, and glucose over 24 hours.

Weekly glucagon‐like peptide‐1 receptor agonist albiglutide as monotherapy improves glycemic parameters in Japanese patients with type 2 diabetes mellitus: A randomized, double‐blind, placebo‐controlled study

The present phase 3, randomized, double‐blind 24‐week study with extension to 1 year assessed the efficacy and safety of albiglutide compared with placebo in Japanese patients with type 2 diabetes mellitus inadequately controlled by diet and exercise with or without a single oral antidiabetic drug.