Optimizing Cardiovascular Outcome in Type 2 Diabetes Mellitus with Better Control of Diabetes Mellitus with Empigliflozin and Hypertension with Renin Angiotensin System Inhibitors and Manidipine Preferably of the Dihydropyridones

Abstract

Aim Obesity is increasing globally by leaps and bounds and thus the incidence of type 2 diabetes mellitus (T2DM) along with it so much so that the term diabesity had to be coined. Earlier we had reviewed how to treat the both together and the role of empagliflozin to improve cardiovascular outcome trials (CVOT). Similarly T2DM and hypertension are pathophysiologically-related diseases which co-exist with a broader complex of metabolic diseases which co-exist possessing similar set of risk factors. Hence it is important to consider which antihypertensives are suitable that possess a positive effect on metabolic factors in cases of T2DM who require an antihypertensive. Method A systematic review was carried out using the PubMed search engine with the MeSH terms: “T2DM”; “essential hypertension; “cardiovascular (CV)”; “Complications of diabetes mellitus (DM) and antihypertensive”; “Antihypertensive preferred in T2DM subjects”; “Renin-angiotensin–aldosterone system inhibitors”; “Angiotensin converting enzyme inhibitors (ACEi)”; “Angiotensin receptor blockers (ARBs)”; “Dihydropyridine calcium channel blocker”; “β2 blockers”; “Diuretics”. Discussion Most diabetes mellitus (DM) subjects need a minimum of two antihypertensive drugs, combining a renin-angiotensinaldosterone system (RAS) inhibitor with a dihydropyridine calcium channel blocker seems to be the most indicated approach. But not all dihydropyridine calcium channel blockers have equivalent effects on metabolic parameters. Hence manidipine that causes positive effect on insulin resistance (IR) seems to be an effective option. We have reviewed how manidipine is superior to amlodipine with regards to improving IR, not seen with amlodipine, along with not causing excessive sympathetic nervous system (SNS) activation, pulse pressure and ankle edema or to much lesser extent than amlodipine. Therefore, manidipine needs to be the first addition to RAS inhibitors in case of DM’s having hypertension of the dihydropyridines calcium channel blockers. Further good blood pressure (BP) control been correlated with good CVs outcomes. Conclusion A RAS inhibitor is the first line of choice of drugs in a subject with T2DM who needs to be treated with empagliflozin for better CVOT outcome, and when a 2nd drug has to be added it is manidipine that is preferred over amlodipine. Plant products are proving to be having a lot of beneficial effects in DM, obesity and hypertension. Thus need for developing agents from plants will prove to be more cost effective in these chronic diseases where compliance is difficult to achieve with the use of common antiDM drugs and antihypertensives with the cost factor along with their side effects.