Exenatide once weekly improved glycaemic control, cardiometabolic risk factors and a composite index of an HbA1c < 7%, without weight gain or hypoglycaemia, over 52 weeks.
OBJECTIVE
Type 2 diabetes mellitus (T2DM) is often associated with cardiovascular (CV) risk factors such as obesity, hypertension and dyslipidemia. The objective of this analysis was to evaluate potential effects of exenatide once weekly (ExQW), a GLP-1 receptor agonist, on glycaemic control and CV risk factors.


METHODS
This analysis included 675 Intent-to-Treat patients with T2DM [baseline (mean ± SD) HbA1c, 8.1 ± 1.2%; fasting blood glucose (FBG), 166 ± 48 mg/dl; weight, 94.3 ± 19.4 kg; systolic/diastolic blood pressure (SBP/DBP), 129 ± 15/78 ± 9 mm Hg; total cholesterol, 178.5 ± 41.9 mg/dl; low-density lipoprotein (LDL), 100.1 ± 35.0 mg/dl; high-density lipoprotein (HDL), 44.5 ± 11.6 mg/dl; triglycerides, 155.6 ± 3.3 mg/dl; alanine aminotransferase (ALT), 32.1 ± 19.5 U/l] treated with diet and exercise alone or in combination with metformin, sulfonylurea, and/or thiazolidinedione who received 52 weeks of ExQW in four clinical trials.


RESULTS
At 52 weeks, ExQW significantly improved HbA1c [mean (SE) change from baseline, -1.3 (0.05)%], FBG [-36.3 (2.02) mg/dl], body weight [-2.6 (0.19) kg], SBP/DBP [-3.6 (0.56) mm Hg/-1.2 (0.34) mm Hg], total cholesterol, -4.4 (1.33) mg/dl; LDL, -2.6 (1.08) mg/dl; HDL, 1.1 (0.31) mg/dl; triglycerides, -7 (1.6)%], and ALT [-4.3 (0.71) IU/l] concentrations, with greater improvements in patients with elevated analyte levels at baseline. Improvements were observed across a range of background antihyperglycaemia therapies. Of patients completing 52 weeks, 19% achieved the composite American Diabetes Association goal (HbA1c < 7.0%, BP < 130/80 mm Hg, LDL < 100 mg/dl), compared to 1% at baseline. Nearly half (48%) achieved HbA1c < 7.0% without weight gain or major/minor hypoglycaemia. Nausea was the most frequent adverse event and was predominantly mild. Hypoglycaemia was infrequent, and more common with a sulfonylurea.


CONCLUSIONS
With 52 weeks of ExQW, patients experienced sustained improvements in glycaemic control and CV risk factors, with an increased likelihood of achieving both a clinically relevant composite outcome (HbA1c < 7% without weight gain or increased risk of hypoglycaemia) and a composite of key therapeutic goals (HbA1c < 7%, BP < 130/80 mm Hg, LDL < 100 mg/dl).
International Diabetes Center, Minneapolis, MN, USA. Richard.Bergenstal@ParkNicollet.com
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RM
Bergenstal
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Li
T K Booker
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Porter
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C
Weaver
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Han
D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000517:prevention & control*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000097:blood / Q000517:prevention & control*; D004334:Drug Administration Schedule; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D055118:Medication Adherence; D008687:Metformin / Q000008:administration & dosage / Q000494:pharmacology; D008875:Middle Aged; D010455:Peptides / Q000008:administration & dosage / Q000494:pharmacology*; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D014688:Venoms / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain
D001786:Blood Glucose; D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D013453:Sulfonylurea Compounds; D014688:Venoms; C517652:hemoglobin A1c protein, human