Effect of Pioglitazone on Body Composition in Asian Indian Diabetics Suggest Role of Limb Fat in their High Insulin Resistance.

Aim: To study (1) effect of pioglitazone mono-therapy on body composition in treatment naive type-2 diabetes mellitus patients and (2) relationship between changes in body composition and insulin resistance induced by pioglitazone. Methods: Subjects: 49 newly diagnosed non-obese T2DM patients were recruited. Design: Open label observational study. Drug and Dose: pioglitazone 30 mg orally once daily for at least 6 months. Exclusion: Primary un-responsiveness at 3 months (10 subjects) and adverse effect (2 subjects). Final analysis done on 37 subjects (Mean age 47.9 years, male:female ratio 20:10) Controls: 37 healthy control subjects (Mean age 47 years M:F ratio 27:10) with normal glucose as per American Diabetes Association criteria. Study parameters were: Plasma glucose, Lipid profile, body mass index, HOMA-R, HOMA-B and body composition measured by dual-energy X-ray absorptiometry (DEXA) at start and after at least 6 months of follow up. Results: Treatment with pioglitazone was associated with significantly decreased glycated hemoglobin (HbA1c), fasting and post-prandial plasma glucose, insulin resistance and triglycerides HDL ratio.Significant increase in total body, limb and head fat mass was observed. The trunk composition did not show significant change. The DEXA Parameters of body composition of diabetics became comparable with controls. Significant correlation was seen between decrease in FPG, PPG, insulin resistance and increase in limb fat mass. Conclusions: Pioglitazone alters body composition by increasing limb and head fat content, without altering trunk fat. Decrease in insulin resistance by it is related to increase in limb fat mass.

Sodium-glucose co-transporter-2 inhibitors as anti-diabetic agents: a review.

The incidence and prevalence of Type 2 diabetes mellitus (T2DM) have been increasing worldwide. However, existing therapeutic classes of anti-diabetic drugs are not adequately effective in achieving and maintaining long-term glycemic control in the most patients. The majority of the drugs control blood sugar without addressing the basic pathology of insulin resistance and relative defi ciency. Moreover, side effects such as hypoglycemia and weight gain, of both new and established drugs need to be considered prior to treating a patient. An emerging anti-hyperglycemic intervention, the sodium glucose co-transporter 2 (SGLT2) inhibitor acts by a novel mechanism. Under physiological conditions, SGLT2 accounts for 90% of the glucose re-absorption in the kidney, while the SGLT2 inhibitors result in an increase in urinary excretion of glucose and lower plasma glucose levels. Here, the pros and cons of SGLT2 inhibitors are considered, while approaching a patient with T2DM. The basic biochemistry and physiology underlying the mechanisms of SGLT2 inhibitors are discussed alongside its clinical pharmacology, with a focus on metabolic changes associated with urinary glucose loss. Finally, a consideration of Food and Drug Administration safety concerns associated with acidosis due to SGLT2 inhibitor usage is presented, to allow a complete understanding of the utility of these molecules in the light of existing T2DM therapies.