Effect of Sodium‐Glucose Cotransport‐2 Inhibitors on Blood Pressure in People With Type 2 Diabetes Mellitus: A Systematic Review and Meta‐Analysis of 43 Randomized Control Trials With 22 528 Patients

Aim To describe population‐level time trends in prescribing patterns of type 2 diabetes therapy, and in short‐term clinical outcomes (glycated haemoglobin [HbA1c], weight, blood pressure, hypoglycaemia and treatment discontinuation) after initiating new therapy. Materials and methods We studied 81 532 people with type 2 diabetes initiating a first‐ to fourth‐line drug in primary care between 2010 and 2017 inclusive in United Kingdom electronic health records (Clinical Practice Research Datalink). Trends in new prescriptions and subsequent 6‐ and 12‐month adjusted changes in glycaemic response (reduction in HbA1c), weight, blood pressure and rates of hypoglycaemia and treatment discontinuation were examined. Results Use of dipeptidyl peptidase‐4 inhibitors as second‐line therapy near doubled (41% of new prescriptions in 2017 vs. 22% in 2010), replacing sulphonylureas as the most common second‐line drug (29% in 2017 vs. 53% in 2010). Sodium‐glucose co‐transporter‐2 inhibitors, introduced in 2013, comprised 17% of new first‐ to fourth‐line prescriptions by 2017. First‐line use of metformin remained stable (91% of new prescriptions in 2017 vs. 91% in 2010). Over the study period there was little change in average glycaemic response and in the proportion of people discontinuing treatment. There was a modest reduction in weight after initiating second‐ and third‐line therapy (improvement in weight change 2017 vs. 2010 for second‐line therapy: −1.5 kg, 95% confidence interval [CI] −1.9, −1.1; P < 0.001), and a slight reduction in systolic blood pressure after initiating first‐, second‐ and third‐line therapy (improvement in systolic blood pressure change 2017 vs. 2010 range: −1.7 to −2.1 mmHg; all P < 0.001). Hypoglycaemia rates decreased over time with second‐line therapy (incidence rate ratio 0.94 per year, 95% CI 0.88, 1.00; P = 0.04), mirroring the decline in use of sulphonylureas. Conclusions Recent changes in prescribing of therapy for people with type 2 diabetes have not led to a change in glycaemic response and have resulted in modest improvements in other population‐level short‐term clinical outcomes.

Section: Discussionmentioning

confidence: 99%

Time trends in prescribing of type 2 diabetes drugs, glycaemic response and risk factors: A retrospective analysis of primary care data, 2010–2017

Dennis

Henley

McGovern

et al. 2019

“…In the present study, we observed marked differences in the baseline characteristics of patients treated with SGLT2 inhibitors or DPP‐4 inhibitors in real‐world settings in Japan, suggesting that SGLT2 inhibitors are often used later in the treatment regimen. We also speculate that clinicians favoured SGLT2 inhibitors in patients with hypertension and obesity in this real‐world setting, after considering the effects of SGLT2 inhibitors on lowering blood pressure and body weight reported in international studies and in Japanese studies . Clinicians might also be delaying SGLT2 inhibitors owing to potential concern about safety .…”

Section: Discussionmentioning

confidence: 96%

Identification of subgroups of patients with type 2 diabetes with differences in renal function preservation, comparing patients receiving sodium‐glucose co‐transporter‐2 inhibitors with those receiving dipeptidyl peptidase‐4 inhibitors, using a supervised machine‐learning algorithm (PROFILE study): A retrospective analysis of a Japanese commercial medical database

Zhou

Watada

Tajima

et al. 2019

Aims To investigate the effects of sodium‐glucose co‐transporter‐2 (SGLT2) inhibitors vs. dipeptidyl peptidase‐4 (DPP‐4) inhibitors on renal function preservation (RFP) using real‐world data of patients with type 2 diabetes in Japan, and to identify which subgroups of patients obtained greater RFP benefits with SGLT2 inhibitors vs. DPP‐4 inhibitors. Methods We retrospectively analysed claims data recorded in the Medical Data Vision database in Japan of patients with type 2 diabetes (aged ≥18 years) prescribed any SGLT2 inhibitor or any DPP‐4 inhibitor between May 2014 and September 2016 (identification period), in whom estimated glomerular filtration rate (eGFR) was measured at least twice (baseline, up to 6 months before the index date; follow‐up, 9 to 15 months after the index date) with continuous treatment until the follow‐up eGFR. The endpoint was the percentage of patients with RFP, defined as no change or an increase in eGFR from baseline to follow‐up. A proprietary supervised learning algorithm (Q‐Finder; Quinten, Paris, France) was used to identify the profiles of patients with an additional RFP benefit of SGLT2 inhibitors vs. DPP‐4 inhibitors. Results Data were available for 990 patients prescribed SGLT2 inhibitors and 4257 prescribed DPP‐4 inhibitors. The proportion of patients with RFP was significantly greater in the SGLT2 inhibitor group (odds ratio 1.27; P = 0.01). The Q‐Finder algorithm identified four clinically relevant subgroups showing superior RFP with SGLT2 inhibitors (P < 0.1): no hyperlipidaemia and eGFR ≥79 mL/min/1.73 m2; eGFR ≥79 mL/min/1.73 m2 and diabetes duration ≤1.2 years; eGFR ≥75 mL/min/1.73 m2 and use of antithrombotic agents; and haemoglobin ≤13.4 g/dL and LDL cholesterol ≥95.1 mg/dL. In each profile, glycaemic control was similar in the two groups. Conclusion SGLT2 inhibitors were associated with more favourable RFP vs. DPP‐4 inhibitors in patients with certain profiles in real‐world settings in Japan.

“…Sodium‐glucose cotransporter 2 inhibitors (SGLT2is), by blocking glucose reabsorption in the kidney, represent a novel approach to reducing hyperglycaemia that is independent of insulin secretion and action . Additional benefits beyond glycaemic control, such as weight loss and reduction in blood pressure, may also play an important role in delaying deterioration of kidney function . Recently, more and more clinical trials, as well as overviews, have evaluated the renal effects of sodium‐glucose cotransporter 2 inhibitors (SGLT2is) and have indicated the possibility of delaying the progression of kidney disease in patients with type 2 diabetes mellitus (T2DM).…”

Section: Introductionmentioning

confidence: 99%

The renoprotective effects of sodium‐glucose cotransporter 2 inhibitors versus placebo in patients with type 2 diabetes with or without prevalent kidney disease: A systematic review and meta‐analysis

Wang

Zhou

Kong

et al. 2019

Aims:We undertook a systematic review and meta-analysis to assess the efficacy and safety of sodium-glucose cotransporter 2 inhibitors (SGLT2is) concerning kidney outcomes in patients with type 2 diabetes mellitus (T2DM), with or without prevalent kidney disease.Materials and Methods: PubMed, Web of science, Embase and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) to assess the efficacy and safety of treatment with SGLT2is versus placebo in patients with T2DM. The weighted mean difference (WMD) and its 95% confidence interval (CI) were applied for continuous variables, and the risk ratio (RR) and corresponding 95% CI were used for dichotomous outcomes. Patients were categorized according to whether the baseline mean estimated glomerular filtration rate (eGFR) was less or was more than 60 mL/min/1.73 m 2 .Results: A total of 25 eligible studies with 43 721 participants were included. There was an initial and small decrease in eGFR during the early treatment period (WMD, −4.63; 95% CI, −6.08 to −3.19 mL/min/1.73 m 2 ), which was noted at 1-6 weeks and gradually narrowed over time, with a decline in protection from eGFR in the long term (WMD, 3.82; 95% CI, 2.80-4.85 mL/min/1.73 m 2 ).SGLT2is significantly delayed albuminuria progression (RR, 0.71; 95% CI, 0.66-0.76), promoted albuminuria regression (RR,1.71; 95% CI, 1.54-1.90), improved the composite of ≥40% decrease in eGFR, in the need for renal-replacement and in death from renal causes (RR, 0.57; 95% CI, 0.49-0.66), and reduced all-cause mortality (RR, 0.84; 95% CI, 0.75-0.94). At the same time, they significantly increased the risk of genital infection (RR, 3.43; 95% CI, 2.87-4.10) vs placebo in patients with T2DM. Meta-regression analyses showed that eGFR-preservation effects were not significantly associated with basic patient characteristics (age, BMI, HbA1c, eGFR level), but were influenced by drug administration (treatment duration, type, dosage of SGLT2is). Subgroup analyses showed that the relative effects on renal outcomes of SGLT2is vs placebo were similar across eGFR subgroups (P heterogeneity >0.05).Conclusions: SGLT2is slowed eGFR decline, lowered albuminuria progression, improved adverse renal endpoints and reduced all-cause mortality, but increased risk of genital infections vs placebo in patients with T2DM. The indication of consistent renal benefits across categories of baseline eGFR levels may allow additional individuals to benefit from SGLT2is therapy.