Exenatide compared with long-acting insulin to achieve glycaemic control with minimal weight gain in patients with type 2 diabetes: results of the Helping Evaluate Exenatide in patients with diabetes compared with Long-Acting insulin (HEELA) study
M J Davies, R Donnelly, A H Barnett, S Jones, C Nicolay, A Kilcoyne, M J Davies, R Donnelly, A H Barnett, S Jones, C Nicolay, A Kilcoyne
Abstract
Aim: The Helping Evaluate Exenatide in overweight patients with diabetes compared with Long-Acting insulin (HEELA) study was designed to examine whether the glucagon-like peptide-1 (GLP-1) receptor agonist, exenatide, could improve HbA1c (< or =7.4%) with minimal weight gain (< or =1 kg) compared with insulin glargine.
Methods: Patients [body mass index (BMI) >27 kg/m(2)] with elevated cardiovascular risk and type 2 diabetes inadequately controlled on two or three oral antidiabetes drugs (OADs) were randomized to add-on exenatide 5-10 microg b.i.d. (n = 118) or insulin glargine o.d. (titrated to target fasting plasma glucose < or =5.6 mmol/l; n = 117) for 26 weeks.
Results: The study population had baseline mean (s.d.) age of 56.5 (9.1) years and BMI of 34.1 (5.3) kg/m(2), and 58.5% of patients were taking two OADs. Mean baseline HbA1c was 8.65 (0.68)% in the exenatide group and 8.48 (0.66)% in the insulin glargine group. The proportions of patients achieving the composite endpoint of HbA1c < or =7.4% with weight gain < or =1 kg were 53.4% for the exenatide group and 19.8% for the insulin glargine group (p < 0.001 for exenatide vs. insulin glargine). Exenatide and insulin glargine did not demonstrate a significant difference in HbA1c improvements [least square (LS) mean [s.e.m.]: -1.25 [0.09]% and -1.26 [0.09]% respectively; p = 0.924], but had divergent effects on body weight (-2.73 [0.31] vs. +2.98 [0.31] kg respectively, p < 0.001) after 26 weeks. There were more treatment-related adverse events with exenatide but a lower incidence of nocturnal hypoglycaemia, with no differences in overall or severe hypoglycaemia.
Conclusions: Additional treatment with exenatide resulted in significantly more overweight and obese patients with an elevated cardiovascular risk and type 2 diabetes achieving better glycaemic control with minimal weight gain compared with insulin glargine.
Figures
References
- Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity related health risk factors, 2001. JAMA. 2003;289:76–79.
- Gæde P, Lund-Andersen H, Parving H-H, Pedersen O. Effect of a multifactorial intervention on mortality in type 2 diabetes. N Engl J Med. 2008;358:580–589.
- American Diabetes Association. Position statement: standards of medical care in diabetes. Diabetes Care. 2009;32(Suppl 1:):S13–S61.
- Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–2443.
- UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33) Lancet. 1998;352:837–853.
- Nathan DM, Buse JB, Davidson MB, et al. Management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy. A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2006;29:1963–1972.
- Raskin PR, Hollander PA, Lewin A, et al. Basal insulin or premix analogue therapy in type 2 diabetes patients. Eur J Intern Med. 2007;18:56–62.
- Holman RR, Thorne KI, Farmer AJ, et al. Addition of biphasic, prandial, or basal insulin to oral therapy in type 2 diabetes. N Engl J Med. 2007;357:1716–1730.
- Riddle MC. Timely initiation of basal insulin. Am J Med. 2004;116(Suppl. 3A:):3S–9S.
- Cvetković RS, Plosker GL. Exenatide: a review of its use in patients with type 2 diabetes mellitus (as an adjunct to metformin and/or a sulfonylurea) Drugs. 2007;67:935–954.
- Barnett A. Exenatide. Expert Opin Pharmacother. 2007;8:2593–2608.
- Barnett AH, Burger J, Johns D, et al. Tolerability and efficacy of exenatide and titrated insulin glargine in adult patients with type 2 diabetes previously uncontrolled with metformin or a sulfonylurea: a multinational, randomized, open-label, two-period, crossover noninferiority trial. Clin Ther. 2007;29:2333–2348.
- Heine RJ, Van Gaal LF, Johns D, et al. Exenatide versus insulin glargine in patients with suboptimally controlled type 2 diabetes: a randomized trial. Ann Intern Med. 2005;143:559–569.
- Glass LC, Qu Y, Lenox S, et al. Effects of exenatide versus insulin analogues on weight change in subjects with type 2 diabetes: a pooled post-hoc analysis. Curr Med Res Opin. 2008;24:639–644.
- Riddle MC, Rosenstock J, Gerich J. The Treat-to-Target Trial: randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetes patients. Diabetes Care. 2003;26:3080–3086.
- UK Department of Health. Quality and Outcomes Framework (updated 2004). Available from URL: Accessed 5 January 2009.
- Goldberg RB, Holman R, Drucker DJ. Clinical decisions: management of type 2 diabetes. N Engl J Med. 2008;358:293–297.
- Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–2471.
- Hermansen K, Davies M, Derezinski T, Martinez Ravn G, Clauson P, Home P. A 26-week, randomized, parallel, treat-to-target trial comparing insulin detemir with NPH insulin as ‘add-on’ therapy to oral glucose-lowering drugs in insulin-naive people with type 2 diabetes. Diabetes Care. 2006;29:1269–1274.
- Wilson PW, D’Agostino RB, Sullivan L, Parise H, Kannel WB. Overweight and obesity as determinants of cardiovascular risk: the Framingham experience. Arch Intern Med. 2002;162:1867–1872.
- Nauck MA, Duran S, Kim D, et al. A comparison of twice-daily exenatide and biphasic insulin aspart in patients with type 2 diabetes who were suboptimally controlled with sulfonylurea and metformin: a non-inferiority study. Diabetologia. 2007;50:259–267.
- Massi Benedetti M, Humburg E, Dressler A, Ziemen M. A one-year, randomized, multicentre trial comparing insulin glargine with NPH insulin in combination with oral agents in patients with type 2 diabetes. Horm Metab Res. 2003;35:189–196.
- The ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560–2672.
- The Action to Control Cardiovascular Risk in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–2559.
- Dluhy RG, McMahon GT. Editorial: Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. 2008;358:2630–2633.
Source: PubMed