Effects of dipeptidyl peptidase‐4 inhibitor linagliptin versus sulphonylurea glimepiride on systemic haemodynamics in overweight patients with type 2 diabetes: A secondary analysis of an 8‐week, randomized, controlled, double‐blind trial

Abstract

Aim To determine the glucose‐independent effect of the dipeptidyl peptidase‐4 (DPP‐4) inhibitor linagliptin versus the sulphonylurea glimepiride on systemic haemodynamics in the fasting and postprandial state in patients with type 2 diabetes (T2D). Materials and Methods In this prespecified secondary analysis of a phase IV, double‐blind trial, 46 metformin‐treated, overweight patients with T2D were included and randomly assigned (1:1) to once‐daily linagliptin (5 mg) or glimepiride (1 mg) for 8 weeks. In a sub‐study involving 26 patients, systemic haemodynamics were also assessed following a standardized liquid meal (Nutridrink Yoghurt style). Systemic haemodynamics (oscillometric device and finger photoplethysmography), arterial stiffness (applanation tonometry) and cardiac sympathovagal balance (heart rate variability [HRV]) were measured in the fasting state and repetitively following the meal. Ewing tests were performed in the fasting state. Results From baseline to week 8, linagliptin compared with glimepiride did not affect systemic haemodynamics, arterial stiffness or HRV in the fasting state. Linagliptin increased parasympathetic nervous activity, as measured by the Valsalva manoeuvre (P = .021) and deep breathing test (P = .027) compared with glimepiride. Postprandially, systolic blood pressure (SBP) dropped an average of 7.6 ± 1.6 mmHg. Linagliptin reduced this decrease to 0.7 ± 2.3 mmHg, which was significant to glimepiride (P = .010). Conclusions When compared with glimepiride, linagliptin does not affect fasting blood pressure. However, linagliptin blunted the postprandial drop in SBP, which could benefit patients with postprandial hypotension.

Postprandial renal haemodynamic effects of the dipeptidyl peptidase‐4 inhibitor linagliptin versus the sulphonylurea glimepiride in adults with type 2 diabetes (RENALIS): A predefined substudy of a randomized, double‐blind trial

“…No treatment differences were observed in postprandial systolic or diastolic blood pressure, MAP, or heart rate at 85 minutes postmeal after 8 weeks of treatment relative to baseline. However, in the current subpopulation, as reported previously, 20 linagliptin blunted maximum postprandial decrease in systolic blood pressure relative to baseline (from À7.8 ± 2.3 mmHg at baseline, to À0.7 ± 2.3 mmHg at week 8; P = .009); this was significant compared with glimepiride (P = .010).…”

“…In a secondary analysis of our trial, linagliptin blunted the meal-induced decrease in blood pressure compared with glimepiride. 20 Seemingly, the linagliptin-induced (relative) increase in postprandial arterial pressure is directly transmitted to the glomerular capillaries, suggesting that DPP-4 inhibition may impair RBF autoregulation, possibly via GLP-1.…”

Potential for Gut Peptide-Based Therapy in Postprandial Hypotension

“…There is limited information about the effects of DPP-4 inhibition on postprandial blood pressure. Reported benefits of DPP-4 inhibitors on PPH relate primarily to case studies, as well as a small cohort of overweight T2D patients receiving metformin therapy [ 50 , 51 , 52 ]. For example, in a comparative study in overweight patients with T2D, 8 weeks treatment with the DPP-4 inhibitor, linagliptin, while achieving comparable glucose-lowering to glimepiride (a sulphonylurea anti-diabetic drug which does not affect haemodynamics), was reported to attenuate the fall in blood pressure after a meal (0.7 ± 2.3 mmHg) without impacting preprandial blood pressure [ 50 ].…”

“…Reported benefits of DPP-4 inhibitors on PPH relate primarily to case studies, as well as a small cohort of overweight T2D patients receiving metformin therapy [ 50 , 51 , 52 ]. For example, in a comparative study in overweight patients with T2D, 8 weeks treatment with the DPP-4 inhibitor, linagliptin, while achieving comparable glucose-lowering to glimepiride (a sulphonylurea anti-diabetic drug which does not affect haemodynamics), was reported to attenuate the fall in blood pressure after a meal (0.7 ± 2.3 mmHg) without impacting preprandial blood pressure [ 50 ]. In contrast, when another DPP-4 inhibitor, vildagliptin, was administered acutely with an intraduodenal glucose infusion in T2D, postprandial SBP and DBP were lower when compared with placebo [ 53 ].…”

Perkembangan Terapi Diabetes Mellitus Tipe 2 Pada Pasien Yang Terinfeksi Covid-19

“…Reseptor DPP4 berinteraksi dengan adenosine deaminase (ADA) pada sel T manusia CD4+ dan CD8+ (Kraaijenhof et al, 2020;Raj et al, 2014). Temuan ini menunjukkan kemungkinan modulasi sistem kekebalan inang oleh SARS-CoV-2, melalui pengikatan ke DPP4 dan bersaing dengan adenosine deaminase (ADA) (Mulvihill & Drucker, 2014;V.…”