aprepitant and Diabetes-Mellitus--Type-2

DPP4 (dipeptidyl peptidase-4) inhibitors comprise a class of oral diabetes medication that have the potential for off-target cardiovascular effects. We previously showed that DPP4 inhibition attenuates the hypotensive effect of acute ACE (angiotensin-converting enzyme) inhibition and increases norepinephrine. Here, we investigated the effects of DPP4 during sustained ACE inhibition compared with during therapy with an ARB (angiotensin receptor blocker) or calcium channel blocker (neutral comparator) in a randomized, double-blinded crossover study.. We enrolled 106 adults with type 2 diabetes and hypertension and 100 received intervention. Subjects were randomized to one of 3 blood pressure arms: ramipril, valsartan, or amlodipine for a total of 15 weeks and received 3 one-week crossover therapies in random order: placebo + placebo, sitagliptin + placebo, and sitagliptin + aprepitant separated by 4-week washout.. We found that DPP4 inhibition increased norepinephrine during ramipril but did not increase blood pressure. Aprepitant, a NK1 (substance P) receptor blocker, lowered standing heart rate during renin-angiotensin-aldosterone system blockade with ramipril or valsartan.. Increased catecholamines during concurrent ACE and DPP4 inhibition may contribute to cardiovascular complications in patients predisposed to heart failure.

Topics: Adult; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Aprepitant; Blood Pressure; Cardiovascular Agents; Catecholamines; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl Peptidase 4; Humans; Norepinephrine; Ramipril; Renin-Angiotensin System; Sitagliptin Phosphate; Valsartan

People with gastroparesis who develop treatment-resistant (refractory) disease pose a difficult challenge, especially in the setting of end-stage renal disease (ESRD) or post pancreas transplant. Aprepitant (a neurokinin-receptor antagonist) is licensed for the short-term treatment of chemotherapy-induced nausea. There is lack of information on its long-term efficacy and safety in people with diabetic gastroparesis.. Case 1 was 73-year-old man with Type 2 diabetes of 25 years' duration and ESRD requiring dialysis. He was referred to our unit as his severe symptoms of gastroparesis had failed to respond to multiple medications and resulted in frequent hospital admissions. Aprepitant, which can be used in ESRD, resulted in significant improvement in his symptoms of nausea and vomiting within weeks, and he remained on this long term (18 months) with continued benefits and had no further gastroparesis-related hospital admissions. Case 2 was a 44-year-old man with Type 1 diabetes of 41 years' duration with a history of severe hypoglycaemic events that required a pancreas transplant. Despite normoglycaemia, his symptoms of gastroparesis persisted and failed to respond to multiple medications and frequent botulinum toxin injections. He was commenced on aprepitant with significant improvement in symptoms and has remained on treatment for 12 months with sustained benefits.. We describe two cases in which long-term aprepitant treatment proved effective in alleviating severe symptoms of gastroparesis that had failed to respond to conventional first-line medical treatments. Our cases highlight the need for novel treatments for managing refractory diabetic gastroparesis.

Topics: Adult; Aged; Aprepitant; Diabetes Mellitus, Type 2; Diabetic Neuropathies; Gastric Emptying; Gastroparesis; Humans; Kidney Failure, Chronic; Male; Morpholines; Pancreas Transplantation; Time Factors; Treatment Outcome