ReviewTherapeutic advances in drug safety2022
Safety of dipeptidyl peptidase-4 inhibitors in older adults with type 2 diabetes: a systematic review and meta-analysis of randomized controlled trials.
Review in Therapeutic advances in drug safety, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 3 of them syntheses that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
13 citing papers in PubMed, 3 syntheses or guidelines pooled it, 17 citations in OpenAlex.
- Safety and efficacy of prusogliptin in type-2 diabetes mellitus: a systematic review and meta-analysis of randomized controlled trials.Irish journal of medical science · 2025Pooled it
- Systematic review of guideline recommendations for older and frail adults with type 2 diabetes mellitus.Age and ageing · 2024Pooled it
- Progress in the treatment of diabetic cardiomyopathy, a systematic review.Pharmacology research & perspectives · 2024Pooled it
- Fotagliptin add-on therapy to metformin in patients with uncontrolled type 2 diabetes: A randomised, multicentre, double-blind, placebo-controlled, phase 3 trial.Diabetes, obesity & metabolism · 2025 · on this mapTrial
- Safety of SGLT2 inhibitors versus DPP-4 inhibitors in super-elderly patients (≥ 80 years) with type 2 diabetes: a propensity score-matched cohort study.Cardiovascular diabetology. Endocrinology reports · 2026Article
- Article
- Real-World Harm Reduction of Metformin Plus DPP4 Inhibitors versus Metformin Plus Sulfonylureas in Older Adults: A Target Trial Emulation Using German Claims Data.Drugs & aging · 2025Article
- Hypoglycemic agents and bone health; an umbrella systematic review of the clinical trials' meta-analysis studies.Diabetology & metabolic syndrome · 2024Review
- Safety and Efficiency of Dipeptidyl Peptidase IV Inhibitors in Patients with Diabetic Kidney Disease: A Systematic Review and Meta-Analysis.Current therapeutic research, clinical and experimental · 2024Review
- Socioeconomic aspects of incretin-based therapy.Diabetologia · 2023Review
- To do one and to get more: Part II. Diabetes and metabolic dysfunction-associated fatty liver diseases.Journal of the Chinese Medical Association : JCMA · 2022Review
- To do one and to get more: Part I. Diabetes and bone.Journal of the Chinese Medical Association : JCMA · 2022Review
- Analysis of acute pancreatitis associated with SGLT-2 inhibitors and predictive factors of the death risk: Based on food and drug administration adverse event report system database.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
registrationPROSPERO: CRD42020210645.
introductionWe aimed to assess the safety of dipeptidyl peptidase-4 (DPP-4) inhibitors in older patients with type 2 diabetes with inadequate glycaemic control.
methodsWe included randomized controlled trials (RCTs) in older (⩾65 years) patients with type 2 diabetes. The intervention group was randomized to treatment with any DPP-4 inhibitors. A systematic search in MEDLINE and Embase was performed in December 2020. For assessing the risk of bias, RoB 2 tool was applied. The quality of evidence was assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We pooled outcomes using random effects meta-analyses.
resultsWe identified 16 RCTs that included 19,317 patients with a mean age of greater than 70 years. The mean HbA1c level ranged between 7.1 and 10.0 g/dl. Adding DPP-4 inhibitors to standard care alone may increase mortality slightly [risk ratio (RR) 1.04; 95% confidence interval (CI) 0.89-1.21]. Adding DPP-4 inhibitors to standard care increases the risk for hypoglycaemia (RR 1.08; 95% CI 1.01-1.16), but difference in overall adverse events is negligible. DPP-4 inhibitors added to standard care may reduce mortality compared with sulfonylureas (RR 0.88; 95% CI 0.75-1.04). DPP-4 inhibitors probably reduce the risk for hypoglycaemia compared with sulfonylureas (magnitude of effect not quantifiable because of heterogeneity) but difference in overall adverse events is negligible. There is insufficient evidence on hospitalizations, falls, fractures, renal impairment and pancreatitis.
conclusionThere is no evidence that DPP-4 inhibitors in addition to standard care decrease mortality but DPP-4 inhibitors increase hypoglycaemia risk. Second-line therapy in older patients should be considered cautiously even in drugs with a good safety profile such as DPP-4 inhibitors. In case second-line treatment is necessary, DPP-4 inhibitors appear to be preferable to sulfonylureas. PLAIN LANGUAGE SUMMARY:
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