Browsing by Author "Seidu, Samuel"

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Benefits and harms of sodium-glucose co-transporter-2 inhibitors (SGLT2-I) and renin-angiotensin-aldosterone system inhibitors (RAAS-I) versus SGLT2-Is alone in patients with type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials
(WILEY, 2022-01-01) Seidu, Samuel; Kunutsor, Setor K.; Topsever, Pinar; Khunti, Kamlesh
Introduction It is uncertain if the combination of sodium-glucose co-transporter 2 inhibitors (SGLT2-Is) and renin-angiotensin-aldosterone system inhibitors (RAAS-Is) provides better cardio-renal clinical outcomes in people with type 2 diabetes mellitus (T2DM) compared with SGLT2-Is alone. Using a systematic review and meta-analysis of randomized controlled trials (RCTs), we evaluated the efficacy and safety with respect to cardio-renal outcomes of the combination of SGLT2 and RAAS inhibitors vs SGLT2-Is in patients with T2DM. Methods Studies were identified from MEDLINE, Embase, the Cochrane Library and search of bibliographies to May 2021. The Cochrane risk of bias tool was used to assess the risk of bias of each study. Study-specific risk ratios (RRs) with 95\% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE. Results Nine articles comprising 8 RCT evaluations (n = 34,551 participants) that compared SGLT2-Is with placebo in patients with T2DM against a background of standard care and reported subgroup results for those treated with or without RAAS-Is at baseline were included. No RCT specifically investigated the combination of SGLT2 and RAAS inhibitors compared with SGLT2-Is alone. The RRs (95\% CIs) for composite cardiovascular outcome and composite CVD death/heart failure hospitalization comparing SGLT2-Is vs placebo in patients on RAAS-Is were 0.93 (0.85-1.01) and 0.88 (0.76-1.02), respectively. The corresponding estimates for patients not on RAAS-Is were 0.78 (0.65-0.93) and 0.73 (0.65-0.82), respectively. There was no evidence of interactions between RAAS-I status and the effects of SGLT2-Is for both outcomes. Single study results showed that SGLT2-Is vs placebo reduced the risk of composite kidney outcome and cardiovascular death in patients with RAAS inhibition. The effect of SGLT2 inhibition vs placebo on kidney parameters, genital infections, volume depletion, hyperkalaemia, hypokalaemia, hypoglycaemia and other adverse events was similar in patients with or without RAAS inhibition. The quality of the evidence ranged from very low to moderate. Conclusions Aggregate published data suggest that the combination of SGLT2 and RAAS inhibitors in the treatment of patients with T2DM may be similar in efficacy and safety if not superior to SGLT2-Is alone. Head-to-head comparisons of the two interventions are warranted to inform T2DM management. The use of SGLT2 inhibition as a first-line therapy in T2DM or its early use in the prevention of renal deterioration and cardiovascular complications in addition to its glycaemic control deserves further study.
Deintensification in older patients with type 2 diabetes: A systematic review of approaches, rates and outcomes
(WILEY, 2019-01-01) Seidu, Samuel; Kunutsor, Setor K.; Topsever, Pinar; Hambling, Clare E.; Cos, Francesc X.; Khunti, Kamlesh
Aim To assess deintensification approaches and rates and evaluate the harm and benefits of deintensification with antidiabetic medication and other therapies among older people (>= 65 years) with type 2 diabetes with or without cardiometabolic conditions. Methods We identified relevant studies in a literature search of MEDLINE, Embase, Web of Science and Cochrane databases to 30 October 2018. Data were extracted on baseline characteristics, details on deintensification and outcomes, and was synthesized using a narrative approach. Results Ten studies (observational cohorts and interventional studies) with data on 26 558 patients with comorbidities were eligible. Deintensification approaches included complete withdrawal, discontinuation, reducing dosage, conversion, or substitution of at least one medication, but the majority of studies were based on complete withdrawal or discontinuation of antihyperglycaemic medication. Rates of deintensification approaches ranged from 13.4\%-75\%. The majority of studies reported no deterioration in HbA1c levels, hypoglycaemic episodes, falls or hospitalizations on deintensification. On adverse events and mortality, no significant differences were observed among the comparison groups in the majority of studies. Conclusion Available but limited evidence suggests that the benefits of deintensification outweigh the harm in older people with type 2 diabetes with or without comorbidities. Given the heterogeneity of patients with diabetes, further research is warranted on which deintensification approaches are appropriate and beneficial for each specific patient population.