Abstract
Background It is uncertain if initial combination therapy with glucose-lowering agents provides longer-term beneficial cardio-renal outcomes compared to stepwise therapy in patients with newly diagnosed type 2 diabetes (T2D). Using a systematic review and meta-analysis of observational cohort studies and randomised controlled trials (RCTs), we evaluated the efficacy and safety of the initial combination therapy vs a stepwise approach in newly diagnosed T2D.
Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE.
Results Eight articles comprising 4 unique RCTs (n=5,527 participants) and one observational cohort study (n=200) that compared initial combination therapy vs stepwise therapy were included. The RR (95% CI) for myocardial infarction comparing initial combination therapy vs stepwise therapy was 1.21 (0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and HbA1c: mean differences (95% CIs) of -0.97 mmol/l (-1.41, -0.53) and -0.13 % (-0.20, -0.07), respectively. Initial combination therapy vs stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition parameters, neuropathy, retinopathy, and adverse events. Single study results showed initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low.
Conclusions Except for improving cardiometabolic and glycaemic parameters, a limited number of studies characterised by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D. Definitive RCTs are warranted.
Methods Studies were identified from MEDLINE, Embase, the Cochrane Library, and search of bibliographies to January 2022. Study-specific risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were pooled. Quality of the evidence was assessed using GRADE.
Results Eight articles comprising 4 unique RCTs (n=5,527 participants) and one observational cohort study (n=200) that compared initial combination therapy vs stepwise therapy were included. The RR (95% CI) for myocardial infarction comparing initial combination therapy vs stepwise therapy was 1.21 (0.74-2.00). Initial combination therapy reduced levels of fasting plasma glucose and HbA1c: mean differences (95% CIs) of -0.97 mmol/l (-1.41, -0.53) and -0.13 % (-0.20, -0.07), respectively. Initial combination therapy vs stepwise therapy reduced lipid levels, blood pressure and intima media thickness, with no differences in body composition parameters, neuropathy, retinopathy, and adverse events. Single study results showed initial combination therapy reduced creatinine levels and urine albumin excretion rate. The quality of the evidence ranged from moderate to very low.
Conclusions Except for improving cardiometabolic and glycaemic parameters, a limited number of studies characterised by small sample sizes show that initial combination therapy for newly diagnosed T2D may be similar in efficacy and safety to stepwise therapy with respect to cardio-renal outcomes. There is a lack of sufficient evidence to recommend initial combination therapy with glucose-lowering agents in newly diagnosed T2D. Definitive RCTs are warranted.
| Original language | English |
|---|---|
| Pages (from-to) | 1469-1482 |
| Number of pages | 14 |
| Journal | Diabetes, Obesity and Metabolism |
| Volume | 24 |
| Issue number | 8 |
| Early online date | 17 Apr 2022 |
| DOIs | |
| Publication status | Published - 1 Aug 2022 |
Bibliographical note
Funding Information:The authors also acknowledge the assistance of Hockley Farm Medical Practice for providing a research environment where research idea was conceived, and for funding the analysis and write‐up.
Funding Information:
information Funded by the National Institute for Health Research (NIHR) Applied Research Collaboration East Midlands (ARC EM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.The authors also acknowledge the assistance of Hockley Farm Medical Practice for providing a research environment where research idea was conceived, and for funding the analysis and write-up.
Publisher Copyright:
© 2022 John Wiley & Sons Ltd.
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