Changes in Insulin Resistance with Different Weight Loss Methods in Patients with Type Two Diabetes Mellitus and Hypertension: A Comparative Clinical Trial

<b>Background:</b> The comparative effects of pharmacological treatment, bariatric surgery, and diet on insulin resistance (IR) remain unclear. <b>Aim:</b> To study the comparative effects of the methods on IR: pharmacologic, bariatric surgery, and very-low-calorie diet (VLCD) in patients with type 2 diabetes mellitus (T2DM) and hypertension. <b>Methods:</b> Design: a 90-day prospective, multicenter, comparative clinical trial including 130 adult patients divided into three groups: Drug, Surgery, and VLCD. Endpoints: HOMA-IR; weight loss; and HbA1c, systolic/diastolic blood pressure (SBP/DBP). <b>Results:</b> At 90 days, weight loss in the Surgery (-19.8%) and VLCD groups (-17.4%) was significant (<i>p</i> < 0.0001), while in the Drug group, the loss was insignificant (-6.5%; <i>p</i> = 0.06). SBP/DBP in the Drug group decreased by -9.5% (<i>p</i> = 0.0002) and -4.1% (<i>p</i> = 0.09), respectively. SBP/DBP in the Surgery group decreased by -13.6% and -10.6%, respectively (<i>p</i> < 0.001), and in the VLCD group, by -23.3% and 21.3%, respectively (<i>p</i> < 0.0001). HOMA-IR in Drug, Surgery, and VLCD groups decreased by -42.2% (<i>p</i> = 0.004), -87.6% (<i>p</i> < 0.0001), and -88.7% (<i>p</i> < 0.0001), respectively. In the Drug group, HOMA-IR did not reach the normal level. Correlation-regression analysis revealed a direct correlation between weight loss and a decrease in HOMA-IR (r = 0.526; F = 33.2, <i>p</i> < 0.0001). HOMA-IR decreases by 65% if weight decreases by 10%; if weight decreases by 25%, then HOMA-IR decreases by 83%. <b>Conclusions:</b> HOMA-IR was associated with weight loss: the greater the weight loss, the lower the HOMA-IR. Weight loss leads to a reduction in the need for antidiabetic/antihypertensive drugs in patients with T2DM and hypertension.