Abstract | AIMS: To compare the cardiovascular, renal and safety outcomes of second-line glucose-lowering agents used in the management of people with type 2 diabetes. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to 13 July 2021 for randomised controlled trials comparing second-line glucose lowering therapies with placebo, standard care or one another. Primary outcomes included cardiovascular and renal outcomes. Secondary outcomes were non-cardiovascular adverse events. Risk ratios (RRs) and corresponding confidence intervals (CI) or credible intervals (CrI) were reported within pairwise and network meta-analysis. The quality of evidence was evaluated using the GRADE (Grading of Recommendations, Assessment, Development and Evaluation) criteria. Number needed to treat (NNT) and number needed (NNH) to harm were calculated at 5 years using incidence rates and RRs. PROSPERO (CRD42020168322). RESULTS: We included 38 trials from seven classes of glucose-lowering therapies. Both sodium- glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide 1 receptor agonists (GLP1RA) showed moderate to high certainty in reducing risk of 3-point major adverse cardiovascular events, 3P-MACE (network estimates: SGLT2i [RR 0.90; 95% CrI 0.84-0.96; NNT, 59], GLP1RA [RR 0.88; 95% CrI 0.83-0.93; NNT, 50]), cardiovascular death, all-cause mortality, renal composite outcome and macroalbuminuria. SGLT2i also showed high certainty in reducing risk of hospitalization for heart failure (hHF), ESRD, acute kidney injury, doubling in serum creatinine and decline in eGFR. GLP1RA were associated with lower risk of stroke (high certainty) while glitazone use was associated with an increased risk of hHF (very low certainty). The risk of developing ESRD was lower with the use of sulphonylureas (low certainty). For adverse events, sulphonylureas and insulin were associated with increased hypoglycaemic events (very low to low certainty), while GLP1RA increased the risk of gastrointestinal side effects leading to treatment discontinuation (low certainty). DPP-4i increased risk of acute pancreatitis (low certainty). SGLT2i were associated with increased risk of genital infection, volume depletion (high certainty), amputation and ketoacidosis (moderate certainty). Risk of fracture was increased with the use of glitazones (moderate certainty). CONCLUSIONS:
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Authors | Ruth Sim, Chun Wie Chong, Navin K Loganadan, Alan Y Y Fong, Leenhapong Navaravong, Zanariah Hussein, Kamlesh Khunti, Shaun Wen Huey Lee |
Journal | Diabetic medicine : a journal of the British Diabetic Association
(Diabet Med)
Vol. 39
Issue 3
Pg. e14780
(03 2022)
ISSN: 1464-5491 [Electronic] England |
PMID | 34962662
(Publication Type: Comparative Study, Journal Article, Meta-Analysis, Systematic Review)
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Copyright | © 2021 Diabetes UK. |
Chemical References |
- Glucagon-Like Peptide-1 Receptor
- Hypoglycemic Agents
- Insulin
- Sodium-Glucose Transporter 2 Inhibitors
- Sulfonylurea Compounds
- Thiazolidinediones
- Metformin
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Topics |
- Cardiovascular Diseases
(mortality)
- Diabetes Mellitus, Type 2
(drug therapy, mortality)
- Glucagon-Like Peptide-1 Receptor
(agonists)
- Humans
- Hypoglycemic Agents
(therapeutic use)
- Insulin
(therapeutic use)
- Kidney Diseases
(mortality)
- Metformin
(therapeutic use)
- Network Meta-Analysis
- Pancreatitis
(mortality)
- Randomized Controlled Trials as Topic
- Sodium-Glucose Transporter 2 Inhibitors
(therapeutic use)
- Sulfonylurea Compounds
(therapeutic use)
- Thiazolidinediones
(therapeutic use)
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