OBJECTIVETo compare the efficacy and safety of weekly albiglutide with daily sitagliptin, daily glimepiride, and placebo. RESEARCH DESIGN AND METHODSPatients 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 HbA 1c from baseline at week 104. Secondary end points included fasting plasma glucose (FPG), weight, and time to hyperglycemic rescue. RESULTSBaseline characteristics were similar among the albiglutide (n = 302), glimepiride (n = 307), sitagliptin (n = 302), and placebo (n = 101) groups. Baseline HbA 1c 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 HbA 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. CONCLUSIONSAdded to metformin, albiglutide was well tolerated; produced superior reductions in HbA 1c and FPG at week 104 compared with placebo, sitagliptin, and glimepiride; and resulted in weight loss compared with glimepiride.

Aims/hypothesis The aim of this study was to compare the efficacy and safety of once-weekly albiglutide with once-daily insulin glargine (A21Gly,B31Arg,B32Arg human insulin) in patients with type 2 diabetes inadequately controlled on metformin with or without sulfonylurea. Methods This was a randomised, open-label, multicentre (n=222), parallel-group, non-inferiority out-patient clinical trial, with 779 patients enrolled in the study. The study was conducted in 222 centres located in four countries. Patients aged ≥18 years with type 2 diabetes treated with metformin (±sulfonylurea) for at least 3 months with a baseline HbA 1c 7.0-10.0% (53.0-85.8 mmol/mol) were randomly assigned (2:1) via a computer-generated randomisation sequence with a voice response system to receive albiglutide (30 mg once a week, n=504) or insulin glargine (10 U once a day, n=241) added to current therapy. Participants and investigators were not masked to treatment assignment. Doses of each medication were adjusted on the basis of the glycaemic response. The primary endpoint was change from baseline in HbA 1c at week 52. Results In the albiglutide group, HbA 1c declined from 8.28± 0.90% (67.0±9.8 mmol/mol) (mean±SD) at baseline to 7.62± 1.12% (59.8±12.2 mmol/mol) at week 52. A similar reduction occurred in the insulin glargine group (8.36±0.95% to 7.55± 1.04% [67.9±10.4 to 59.0±11.4 mmol/mol]). The modeladjusted treatment difference of 0.11% (95% CI −0.04%, 0.27%) (1.2 mmol/mol [95% CI −0.4, 3.0 mmol/mol]) indicated non-inferiority of albiglutide to insulin glargine based on the pre-specified non-inferiority margin of 0.3% (3.3 mmol/mol, p=0.0086). Body weight increased in the insulin glargine group and decreased in the albiglutide group, with a mean treatment difference of −2.61 kg (95% CI −3.20, −2.02; p<0.0001). Documented symptomatic hypoglycaemia occurred in a higher proportion of patients in the insulin glargine group than in the albiglutide group (27.4% vs 17.5%, p=0.0377). Conclusions/interpretation Albiglutide was non-inferior to insulin glargine at reducing HbA 1c at week 52, with modest weight loss and less hypoglycaemia. Both drugs were well tolerated. Albiglutide may be considered an alternative to insulin glargine in this patient population. Trial registration: ClinicalTrials.gov NCT00838916 (completed) Funding: This study was planned and conducted by GlaxoSmithKline.

Albiglutide 30 mg administered once weekly as an add-on to pioglitazone (with or without metformin) provided effective and durable glucose lowering and was generally well tolerated.

RSGMET provided similar short-term glycaemic control to MET with greater improvements in estimates of insulin sensitivity, B-cell function and CRP, with less diarrhoea and low risk of biochemical hypoglycaemia, suggesting that early use of combination therapy may be appropriate.

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