Quantifying the effects of diuretics and β‐adrenoceptor blockers on glycaemic control in diabetes mellitus – a systematic review and meta‐analysis

Abstract

AIMSAlthough there are reports that β-adrenoceptor antagonists (beta-blockers) and diuretics can affect glycaemic control in people with diabetes mellitus, there is no clear information on how blood glucose concentrations may change and by how much. We report results from a systematic review to quantify the effects of these antihypertensive drugs on glycaemic control in adults with established diabetes. METHODSWe systematically reviewed the literature to identify randomized controlled trials in which glycaemic control was studied in adults with diabetes taking either beta-blockers or diuretics. We combined data on HbA1c and fasting blood glucose using fixed effects meta-analysis. RESULTSFrom 3864 papers retrieved, we found 10 studies of beta-blockers and 12 studies of diuretics to include in the meta-analysis. One study included both comparisons, totalling 21 included reports. Beta-blockers increased fasting blood glucose concentrations by 0.64 mmol l −1 (95% CI 0.24, 1.03) and diuretics by 0.77 mmol l −1 (95% CI 0.14, 1.39) compared with placebo. Effect sizes were largest in trials of non-selective beta-blockers (1.33, 95% CI 0.72, 1.95) and thiazide diuretics (1.69, 95% CI 0.60, 2.69). Beta-blockers increased HbA1c concentrations by 0.75% (95% CI 0.30, 1.20) and diuretics by 0.24% (95% CI −0.17, 0.65) compared with placebo. There was no significant difference in the number of hypoglycaemic events between beta-blockers and placebo in three trials. CONCLUSIONSRandomized trials suggest that thiazide diuretics and non-selective beta-blockers increase fasting blood glucose and HbA1c concentrations in patients with diabetes by moderate amounts. These data will inform prescribing and monitoring of beta-blockers and diuretics in patients with diabetes.

Association of Thiazide‐Type Diuretics With Glycemic Changes in Hypertensive Patients: A Systematic Review and Meta‐Analysis of Randomized Controlled Clinical Trials

“…Diabetic patients receiving thiazides were shown to have a moderate increase in serum glucose. A recent meta‐analysis reported a higher increase in FPG (MD, 1.69 mmol/L [30.42 mg/dL]; 95% CI, 0.69–2.69) in diabetic patients taking thiazide diuretics compared with that in our study. Considering the impaired glucose metabolism of existing diabetes, it can be assumed that the use of thiazides in diabetic patients needs to be more cautiously monitored.…”

Medications affecting glycemic control

“…However, Increasing FBG, NODM, and increasing hemoglobin A1c (A1C) have been linked to βB use [21]. The overall magnitude of FBG increase appears to be minor (0.6 mmol/L for pooled endpoint FBG) based on a meta-analysis of data from 1889 patients with DM [21].…”

“…The overall magnitude of FBG increase appears to be minor (0.6 mmol/L for pooled endpoint FBG) based on a meta-analysis of data from 1889 patients with DM [21]. Non-selective βB had a greater effect than selective βB (1.3 mmol/L and 0.15 mmol/L increases, respectively) in this meta-analysis although the literature as a whole is inconsistent [10,[21][22][23][24]. Data are also inconsistent for NODM with βB use.…”

“…The extent to which βB-associated glycemic effects may diminish the known cardiovascular benefits of βB is uncertain. Therefore, it is recommended to prescribe or continue βB in DM patients as indicated while closely monitoring their BG and adjusting therapy for glucose management, if necessary [21].…”

Novel targets for the development of drugs for Type 2 Diabetes Mellitus

“…Besides changes in expression of STK39/SPAK, it has been observed that STK39/SPAK and its substrate NCC (Na-Cl co-transporter), are highly phosphorylated in hyperinsulinemic db/db mice compared to non-diabetic db/db mice (Nishida et al, 2012), indicating a role for STK39 and NCC in the development of T2DM. In addition, clinical studies with the NCC specific inhibitor, thiazide, used to prevent high blood pressure, showed that patients with diabetes increase their fasting glucose and decrease their insulin sensitivity after administration of thiazide, indeed suggesting that the WNK/SPAK/NCC-pathway is involved in increasing insulin resistance (Eriksson et al, 2008;Hirst et al, 2015). Besides affecting NCC, STK39/SPAK can also inactivate the chloride-transporter CFTR, which is involved in Cystic Fibrosis (Yang et al, 2011).…”