HOMA-S is associated with greater HbA1c reduction with a GLP-1 analogue in patients with type 2 diabetes.
Exenatide, a glucagon-like peptide-1 (GLP-1) analogue, is an effective glucoregulator for treating overweight individuals, not at target HbA1 c. This prospective study aimed to determine whether estimates of beta cell function (HOMA-B) and insulin sensitivity (HOMA-S) predict response to Exenatide treatment.Prospective data on 43 type 2 diabetes patients were collected for up to 2.8 years in UK primary care. HOMA-B and HOMA-S were estimated prior to initiating Exenatide, with monitoring of cardio-metabolic risk factors.Mean (SD) age and BMI pre-treatment were 54.1±10.5 years and 35.7±7.5 kg/m2 respectively. HbA1c decreased (mean reduction 0.9%, p=0.04; p for trend=0.01) in 61% of patients. In univariate analyses, HOMA-S as a measure of insulin sensitivity was inversely (β=- 0.41, p 0.009) related to change in HbA1c, with no relation for HOMA-B.In a random effects regression model that included age at baseline, weight, LDL-C, HDL-C and triglycerides, change in HbA1c (β= - 0.14, p<0.001) and HDL-C (β= - 0.52, p=0.011) were independently associated with increasing insulin sensitivity (r2=0.52). Thus patients with greater measured insulin sensitivity achieved greater reduction in HbA1c independent of the factors described above.In logistic regression those in the highest tertile of log-HOMA-S were 45% more likely to have a fall in HbA1c with an odds ratio (OR) of 0.55 (95% CI 0.47-0.66) p<0.0001 (log likelihood ratio for the model χ2=71.6, p<0.0001).Patients with greater measured insulin sensitivity achieve greater reduction in HbA1c with Exenatide. Determination of insulin sensitivity may assist in guiding outcome expectation in overweight patients treated with GLP-1 analogues.
Department of Medicine, Leighton Hospital, Crewe, UK. adrian.heald@manchester.ac.uk
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AH
Heald
R P
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Narayanan
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D
Lowes
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Jarman
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E
Onyekwelu
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Qureshi
I
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Laing
S G
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Anderson
D015992:Body Mass Index; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives*; D006442:Glycated Hemoglobin / Q000032:analysis*; D006706:Homeostasis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D050417:Insulin-Secreting Cells / Q000502:physiology; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D010455:Peptides / Q000627:therapeutic use; D011446:Prospective Studies; D016896:Treatment Outcome; D014688:Venoms / Q000627:therapeutic use
D000077270:Exenatide; D052216:Glucagon-Like Peptide 1; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D010455:Peptides; D014688:Venoms