A recent study showed that in patients with diabetic nephropathy the addition of finerenone to an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker improved urinary albumin-creatinine ratio better than placebo [ 87 ]. It seems that aldosterone antagonists have a renoprotective effect that is independent of systemic hemodynamic alterations [ 88 ]. Diabetic individuals tend to develop type 4 renal tubular acidosis and therefore hyperkalemia may be a concern in those treated with aldosterone antagonists, particularly when combined with ACEIs or ARBs, although the long-term risk is low [ 89 ].
More than two-thirds of hypertensive individuals are inadequately controlled on mono therapy [ 90 ]. Most diabetic individuals are treated with RAAS inhibitors and most guidelines recommend adding a calcium antagonist or diuretic as add-on therapy [ 1 , 5 , 6 ].
The superiority of amlodipine over hydrochlorothiazide as an addition to benazepril disappeared in obese individuals [ 91 ]. Based on these studies, it seems that CCBs are appropriate as second-line agents in diabetic patients already treated with RAAS blockers. In obese individuals or when volume overload is present, diuretics may be used as well. In a large group of patients with stage I hypertension a combination of chlorthalidone and amiloride yielded a greater reduction in BP than the ARB losartan [ 94 ].
In patients requiring triple therapy, RAAS blockers should be combined with diuretics and CCBs, unless there is compelling indication for the use for a different anti-hypertensive class heart failure or ischemic heart disease for beta blockers or benign prostate hyperplasia for alpha blockers. Patients with resistant hypertension, particularly in the presence of low potassium levels, may benefit from aldosterone antagonists. These should be used cautiously, particularly in patients already on RAAS blockers.
Once BP goal has been achieved antihypertensive treatment should be continued. In the ADVANCE trial discontinuation of antihypertensive medications was associated with increased risk of combined macro and microvascular events [ 95 ]. In the last decade there is a surge of new anti-diabetic medications working on different pathways in insulin production and glucose disposal.
Some of these agents have beneficial effects on BP and may prove as important agents for the control of hypertension in diabetic individuals. In this paragraph we will discuss these classes of agents and the evidence for their effect on elevated BP in both normotensive and hypertensive individuals. Glucagon-like-polypeptide 1 analogues GLP1a lead to a clinically significant weight loss in both diabetics and non-diabetics [ 96 , 97 ] and thus may aid in a better BP control.
On the other hand, they have been reported to increase heart rate through sympathetic nervous system activation [ 98 ] and this may result in BP elevation. Thus it seems the GLP1a have a neutral effect on BP and may even result in a mild decrease in BP, but probably cannot serve as an alternative to anti-hypertensive treatment in hypertensive diabetics.
DPP4 inhibitors elevate endogenous GLP1 through inhibition of the endogenous substance responsible for its degradation.
Several studies reported that these agents produce a modest decrease in BP [ — ], others reported that they increase BP [ ] and yet others reported that they negate the hypotensive effects of ACEI [ ]. Overall it seems that DPP4 inhibitors are neutral in term of BP control and their initiation probably does not significantly affect BP control.follow link
Pharmacologic Management of Hypertension in Patients with Diabetes - American Family Physician
Three representatives of this new class of anti-diabetics are currently in the market-canagliflozin, dapagliflozin and empagliflozin. Some others are under development. Although agents differ in their affinity for the sodium-glucose transporter, their clinical efficacy is quite similar. All three have similar efficacy in terms of glucose control and all are associated with significant weight loss [ ].
A pooled analysis of studies of canagliflozin and dapagliflozin concluded that orthostatic hypotension was not increased during treatment with these SGLT2 inhibitors compared with placebo. Three independent studies published after this meta-analysis specifically evaluated the effect of SGLT2 inhibitors on BP in diabetic individuals.
The dapagliflozin BP study [ ] reported a 4. Orthostatic hypotension was not increased in the treatment arm compared with placebo. In another study Weber MA et al. Patients who entered the study with uncontrolled hypertension had a more significant response to empagliflozin compared with those in which BP was well controlled prior to study initiation.
Orthostatic hypotension was more prevalent in the empagliflozin group, but none of the patients who had orthostatic hypotension experienced clinical events related to this finding, making its clinical significance questionable. Orthostatic hypertension as assessed by ambulatory BP monitoring or through clinical symptoms occurred only in the canagliflozin group. It is important to note that patients enrolled to all three studies of SGLT2 inhibitors in hypertensive diabetics were Caucasian and data evaluating the influence of SGLT inhibitors on BP in diabetics of non-Caucasian origin is much less extensive.
Hypertension Management in Older and Frail Older Patients
In addition, these drugs were reported to have a positive effect on the circadian rhythm in rats who developed hypertension [ ]. This class of agents is certainly promising as it can be used to control glucose, weight and BP. Current evidence does not support a more stringent BP control strategy for all diabetic patients and the evidence to support stringent control in certain diabetic patients is also inconclusive.
This is reflected in recommendations in most current BP treatment guidelines. The choice of anti-hypertensive agent is supported by minimal evidence although RAAS blockers are usually used as first-line agents. When requiring more than one agent for the control of hypertension in diabetics, calcium antagonists or diuretics are probably appropriate as second line agents. In addition to lowering BP it is very important to control all other risk factors in diabetic patients.
This heterogeneous treatment model, relates directly to general trends in modern medicine, reflecting an aspiration for individually tailored medicine, adapted specifically for the particular demographic and biologic characteristics of each patient.
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Intensifying diabetes treatment with oral medicines
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Case study: Frail elderly patient with type 2 diabetes - Intensify monotherapy
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