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

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 (≤7.4%) with minimal weight gain (≤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 μg b.i.d. (n = 118) or insulin glargine o.d. (titrated to target fasting plasma glucose ≤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 ≤7.4% with weight gain ≤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.

Shown for reading. Its publisher allows quoting it, not republishing it.

References 25

1. 1.

   Mokdad AH, Ford ES, Bowman BA, et al. Prevalence of obesity, diabetes, and obesity related health risk factors, 2001. JAMA. 2003;289:76-79.

   Not in our library10.1001/jama.289.1.76

2. 2.

   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.

   Not in our library10.1056/nejmoa0706245

3. 3.

   Position statement: standards of medical care in diabetes. Diabetes Care. 2009;32(Suppl 1:):S13-S61.

   Not in our library10.2337/dc09-s013

4. 4.

   Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427-2443.

   Not in our library10.1056/nejmoa066224

5. 5.

   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.

   Not in our library

6. 6.

   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.

   Not in our library10.2337/dc06-9912

7. 7.

   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.

   Not in our library10.1016/j.ejim.2006.09.006

8. 8.

   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.

   Not in our library10.1056/nejmoa075392

9. 9.

   Riddle MC. Timely initiation of basal insulin. Am J Med. 2004;116(Suppl. 3A:):3S-9S.

   Not in our library10.1016/j.amjmed.2003.12.003

10. 10.

    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.

    Not in our library10.2165/00003495-200767060-00008

11. 11.

    Barnett A. Exenatide. Expert Opin Pharmacother. 2007;8:2593-2608.

    Not in our library10.1517/14656566.8.15.2593

12. 12.

    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.

    Not in our library10.1016/j.clinthera.2007.11.006

13. 13.

    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.

    Not in our library10.7326/0003-4819-143-8-200510180-00006

14. 14.

    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.

    Not in our library10.1185/030079908x260862

15. 15.

    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.

    Not in our library10.2337/diacare.26.11.3080

16. 16.

    This reference’s wording can’t be shown under the paper’s licence.

    Not in our library

17. 17.

    Goldberg RB, Holman R, Drucker DJ. Clinical decisions: management of type 2 diabetes. N Engl J Med. 2008;358:293-297.

    Not in our library10.1056/nejmclde0708469

18. 18.

    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.

    Not in our library10.1056/nejmoa072761

19. 19.

    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.

    Not in our library10.2337/dc05-1365

20. 20.

    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.

    Not in our library10.1001/archinte.162.16.1867

21. 21.

    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.

    Not in our library10.1007/s00125-006-0510-2

22. 22.

    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.

    Not in our library10.1055/s-2003-39080

23. 23.

    Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med. 2008;358:2560-2672.

    Not in our library10.1056/nejmoa0802987

24. 24.

    Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.

    Not in our library10.1056/nejmoa0802743

25. 25.

    Dluhy RG, McMahon GT. Editorial: Intensive glycemic control in the ACCORD and ADVANCE trials. N Engl J Med. 2008;358:2630-2633.

    Not in our library10.1056/nejme0804182

Cited by papers we hold 1

• The Effect of Glucagon-Like Peptide 1 Receptor Agonists on Weight Loss in Type 2 Diabetes: A Systematic Review and Mixed Treatment Comparison Meta-Analysis · 2015
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.