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Objective: The Qatar Study was designed to examine the efficacy of combination therapy with exenatide plus pioglitazone versus basal/bolus insulin in patients with long-standing poorly controlled type 2 diabetes mellitus (T2DM) on metformin plus a sulfonylurea., Research Design and Methods: The study randomized 231 patients with poorly controlled (HbA 1c >7.5%, 58 mmol/mol) T2DM on a sulfonylurea plus metformin to receive 1 ) pioglitazone plus weekly exenatide (combination therapy) or 2 ) basal plus prandial insulin (insulin therapy) to maintain HbA 1c <7.0% (53 mmol/mol)., Results: After a mean follow-up of 12 months, combination therapy caused a robust decrease in HbA 1c from 10.0 ± 0.6% (86 ± 5.2 mmol/mol) at baseline to 6.1 ± 0.1% (43 ± 0.7 mmol/mol) compared with 7.1 ± 0.1% (54 ± 0.8 mmol/mol) in subjects receiving insulin therapy. Combination therapy was effective in lowering the HbA 1c independent of sex, ethnicity, BMI, or baseline HbA 1c . Subjects in the insulin therapy group experienced significantly greater weight gain and a threefold higher rate of hypoglycemia than patients in the combination therapy group., Conclusions: Combination exenatide/pioglitazone therapy is a very effective and safe therapeutic option in patients with long-standing poorly controlled T2DM on metformin plus a sulfonylurea., (© 2017 by the American Diabetes Association.)

Aim: To examine the efficacy of glucose‐lowering medications in subgroups of patients with type 2 diabetes mellitus (T2DM). Research design and methods: Cluster analysis was performed in participants in the Efficacy and Durability of Initial Combination Therapy for Type 2 Diabetes (EDICT) study and the Qatar study using age, body mass index (BMI), glycated haemoglobin (HbA1c), and homeostatic model assessment of insulin resistance (HOMA‐IR) and beta‐cell function (HOMA‐β). Participants also underwent an oral glucose tolerance test with measurement of plasma glucose, insulin and C‐peptide concentrations to derive independent measures of insulin secretion and insulin sensitivity. The response to glucose‐lowering therapies (change in HbA1c) was measured in each participant cluster for 3 years. Results: Three distinct and comparable clusters/groups of T2DM patients were identified in both the EDICT and Qatar studies. Participants in Group 1 had the highest HbA1c and manifested severe insulin deficiency. Participants in Group 3 had comparable insulin sensitivity to those in Group 1 but better beta‐cell function and better glucose control. Participants in Group 2 had the highest BMI with severe insulin resistance accompanied by marked hyperinsulinaemia, which was primarily attributable to decreased insulin clearance. Unexpectedly, participants in Group 1 had better response to combination therapy with pioglitazone plus exenatide than with insulin therapy or metformin sequentially followed by glipizide and basal insulin, while participants in Group 2 responded equally well to both therapies despite very severe insulin resistance. Conclusion: Distinct metabolic phenotypes characterize different T2DM clusters and differential responses to glucose‐lowering therapies. Participants with severe insulin deficiency respond better to agents that preserve beta‐cell function, while, surprisingly, patients with severe insulin resistance did not respond favourably to insulin sensitizers. [ABSTRACT FROM AUTHOR]

The present study aims to identify predictors for response to combination therapy with pioglitazone plus exenatide vs basal/bolus insulin therapy in T2DM patients who are poorly controlled with maximum/near‐maximum doses of metformin plus a sulfonylurea. Participants in the Qatar study received a 75‐g OGTT with measurement of plasma glucose, insulin and C‐peptide concentration at baseline and were then randomized to receive either treatment with pioglitazone plus exenatide or basal/bolus insulin therapy for one year. Insulin secretion measured with plasma C‐peptide concentration during the OGTT was the strongest predictor of response to combination therapy (HbA1c ≤ 7.0%) with pioglitazone plus exenatide. A 54% increase in 2‐hour plasma C‐peptide concentration above the fasting level identified subjects who achieved the glycaemic goal (HbA1c < 7.0%) with 82% sensitivity and 79% specificity. Only baseline HbA1c was a predictor of response to basal/bolus insulin therapy. Thus, the increment in 2‐hour plasma C‐peptide concentration above the fasting level provides a useful tool to identify poorly controlled T2DM patients who can achieve glycaemic control without insulin therapy, and thereby, can be used to individualize antihyperglycaemic therapy in poorly controlled T2DM patients. [ABSTRACT FROM AUTHOR]

A correction to the article "Combination Therapy With Exenatide Plus Pioglitazone Versus Basal/Bolus Insulin in Patients With Poorly Controlled Type 2 Diabetes on Sulfonylurea Plus Metformin: The Qatar Study" that was published in the issue of "Diabetes Care" is presented.