Sitagliptin improves diastolic cardiac function but not cardiorespiratory fitness in adults with type 2 diabetes

Abstract

Background.-People with type 2 diabetes mellitus (T2D) have preclinical cardiac and vascular dysfunction that predicts low cardiorespiratory fitness (CRF). CRF is a powerful predictor of cardiovascular mortality, a primary concern in T2D management. Glucagon-like pepetide-1 (GLP-1) augments cardiovascular function and our previous data in rodents demonstrate that potentiating the GLP-1 signal with a dipeptidyl peptidase-4 (DPP4) inhibitor augments CRF. We hypothesized that administration of a DPP4-inhibitor (sitagliptin) would improve CRF in adults with T2D. Methods and Results.-Thirty-eight participants (64±1 years; mean±SE) with T2D were randomized in a double-blinded study to receive 100mg/day sitagliptin, 2mg/day glimepiride, or placebo, for 3 months after baseline measurements. Fasting glucose decreased with both glimepiride and sitagliptin compared with placebo (P=0.002). CRF did not change in any group (Placebo: Pre: 15.4±0.9 vs. Post: 16.1±1.1 ml/kg/min vs. Glimepiride: 18.5±1.0 vs. 17.7±1.2 ml/kg/min vs. Sitaglipin: 19.1±1.2 vs. 18.3±1.1 ml/kg/min; P=0.3). Sitagliptin improved cardiac diastolic function, however, measures of vascular function did not change with any treatment. Conclusions.-Three months of sitagliptin improved diastolic cardiac function, however, CRF did not change. These data suggest the need to incorporate aerobic exercise in the management of T2D to improve CRF and reduce the risk of premature cardiovascular mortality.

Retracted: Effect of dipeptidyl peptidase‐4 inhibitors on the progression of atherosclerosis in patients with type 2 diabetes mellitus: A meta‐analysis of randomised controlled trials

“…64 In addition, the use of renin-angiotensin system blockers to strictly control blood pressure, and the use of statins to control cholesterol can reduce the progression of arterial stiffness in this population. 37 A new type of hypoglycaemic drug, SGLT2 inhibitor, can effectively reduce blood pressure in patients who have T2DM, which is derived from its natriuretic effect. 65 Through subgroup analysis, we found that DPP-4Is have a better efficacy on reducing CIMT in T2DM patients without cardiovascular diseases.…”

Impact of novel glucose‐lowering therapies on physical function in people with type 2 diabetes: A systematic review and meta‐analysis of randomised placebo‐controlled trials

“…Across the 11 included manuscripts, data from 6886 individuals (3860 in intervention; 3026 in placebo) from diverse populations, with majority being white (78.9%) are included in this review (Table 1). Two studies did not provide ethnicity data 41,42 . The number randomised varied from a minimum of 23 participants 41 to a maximum of 3297 participants 43 .…”

“…The number randomised varied from a minimum of 23 participants 41 to a maximum of 3297 participants 43 . The weighted mean age of the participants was 61 years and mean duration of diabetes was 11.9 years although this information was missing for one study 42 …”

“…43 The weighted mean age of the participants was 61 years and mean duration of diabetes was 11.9 years although this information was missing for one study. 42 The included studies reported five different physical function outcomes as summarised in Table 2. These ranged from self-reported subjective measures of physical function including SF-36, 44 Impact of Weight on Quality of Life-Lite (IWQOL-Lite) 45 and Ability to Perform Physical Activities of Daily Living (APPADL) questionnaire 46 to objectively assessed measures of physical activity (sixminute walk test, 6MWT) 47 and cardiorespiratory fitness (maximal oxygen uptake, VO 2max ).…”

Mechanistic Causes of Reduced Cardiorespiratory Fitness in Type 2 Diabetes

“…They also had attenuated vascular adaptation to exercise training [ 85 ]. However, in people with T2D, sitagliptin improved diastolic cardiac function, but not CRF, in the absence of formal exercise training [ 89 ]. Similarly, in people with T2D, treatment with exenatide, a GLP-1 agonist, improved diastolic heart function and arterial stiffness, but did not improve CRF in the absence of formal exercise training [ 90 ].…”