Linagliptin 5mg tablets

Abstract Background Type 2 diabetes mellitus (T2DM) is one of the most consequential drivers of premature death globally, largely through its acceleration of cardiovascular and renal disease. Dipeptidyl peptidase-4 (DPP-4) inhibitors have become a major cornerstone of second-line glucose-lowering therapy, valued for their glycemic efficacy, weight neutrality, and low hypoglycemia risk. Whether these attributes translate into a tangible mortality advantage over comparators, however, has not yet been consistently demonstrated across the trial literature. Objectives To evaluate the mortality benefits of DPP-4 inhibitors compared with placebo or other oral hypoglycemic agents (OHAs) in adults with T2DM, using only evidence from randomized controlled trials published between 2015 and 2025. Methods A pre-registered systematic review was conducted in line with PRISMA 2020 reporting standards (PROSPERO: CRD420251108505). PubMed and Embase were searched from January 2015 to January 2025 for RCTs enrolling adult T2DM patients randomized to a DPP-4 inhibitor versus placebo or an alternative OHA, with mortality as a reported endpoint. Two independent reviewers performed screening, data extraction, and risk-of-bias assessment (Cochrane RoB 2.0). Certainty of evidence was graded using the GRADE framework. Given substantive clinical heterogeneity, data were synthesized descriptively rather than pooled in a formal meta-analysis. Results Sixty-six records were retrieved across both databases. After removing 11 duplicates, 55 records were screened; 33 were excluded at title and abstract review. Twenty-two full texts were assessed, of which 8 were excluded for methodological or eligibility reasons, leaving 14 studies in the qualitative synthesis. These included the four major cardiovascular outcome trials (CVOTs): SAVOR-TIMI 53 (saxagliptin), EXAMINE (alogliptin), TECOS (sitagliptin), and CARMELINA (linagliptin vs. placebo), alongside CAROLINA (linagliptin vs. glimepiride) and additional RCTs and RCT-level meta-analyses. Across all CVOTs, all-cause mortality hazard ratios ranged from 0.97 to 1.11, none reaching statistical significance. Cardiovascular mortality was similarly neutral across trials. A notable outlier was the hospitalization-for-heart-failure signal in SAVOR-TIMI 53, which was not replicated in subsequent trials. Risk of bias was rated low in CVOTs and some concerns to high in smaller trials. Overall certainty of evidence for mortality outcomes was rated moderate by GRADE. Conclusion DPP-4 inhibitors are cardio-vascularly safe, but they do not appear to confer a statistically significant reduction in all-cause or cardiovascular mortality compared with placebo or active OHAs. Their clinical value lies in tolerability, hypoglycemia sparing, and suitability for complex patient populations rather than in mortality superiority. Larger, longer-term trials inclusive of low-income country populations, where sulphonyl-ureas remain the dominant comparator, are needed to resolve remaining uncertainty. PROSPERO Registration: CRD420251108505 Clinical trial number: not applicable.

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Inhibitors of dipeptidyl peptidase-4 (DPP-4) enzyme are one of the commonly recommended hypoglycemic agents. Although efficient in controlling hyperglycemia, their cardiovascular (CV) safety has been debated for long-term use, particularly in relation to heart failure risk. This review analyzed the cardiovascular safety profile after the consumption of various DPP-4 inhibitors in hyperglycemic patients. The systematic review and meta-analysis was conducted by utilizing widespread empirical research and randomized control trials (RCTs), evaluating sitagliptin, saxagliptin, alogliptin, and linagliptin. Databases searched included PubMed, Embase, Cochrane CENTRAL, and Clinical Trials.gov through September 2025. Outcomes assessed were: HHF, i.e., hospitalization for heart failure, MACE, i.e., major adverse cardiovascular events (CV death, nonfatal myocardial infarction (MI), nonfatal cerebrovascular attack (CVA), all-cause mortality, and cardiovascular mortality. Random-effects metHFa-analyses were conducted, with heterogeneity assessed via I² statistics. Seven large RCTs (n > 70,000 participants) were included, along with supporting observational data. Pooled analysis demonstrated no significant increase in MACE intake of DPP-4 inhibitors when compared to placebo (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.93-1.05, heterogeneity (I²) = 5%). However, an increased probability of HHF was found (HR 1.14, 95% CI 1.02-1.27, I² = 28%), largely driven by saxagliptin (HR 1.27, 95% CI 1.07-1.51) and, to a lesser extent, alogliptin. While no significant heart failure (HF) risk was observed by the intake of drugs sitagliptin (HR 1.00, 95% CI 0.83-1.20) and linagliptin (HR 1.02, 95% CI 0.89-1.17), no differences were noted in all-cause or CV mortality across the class. DPP-4 inhibitors, as a group of drugs, are safe with respect to MACE, but saxagliptin and possibly alogliptin are linked with an increased risk of HHF. Sitagliptin and linagliptin appear neutral regarding HF risk. These findings highlight the importance of drug-specific evaluation when selecting a DPP-4 inhibitor for type-2 diabetic patients, particularly those having an elevated risk of heart failure.

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Dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium–glucose cotransporter 2 (SGLT2) inhibitors are widely prescribed for their cardiometabolic benefits, yet their hematologic oncologic safety remains uncertain. Because hematologic malignancies are highly lethal and biologically heterogeneous, delineating drug-specific risks across histopathologic subtypes is clinically crucial. This histopathology-stratified network meta-analysis (NMA) evaluated and compared the hematologic malignancy risks associated with individual agents from these drug classes. Following Cochrane guidance for adverse-event synthesis, we conducted this frequentist-based NMA of randomized controlled trials (RCTs). The primary endpoint was incident hematologic malignancy, categorized a priori into leukemia (acute and chronic forms), lymphoma (Hodgkin and non-Hodgkin), and myeloma/plasma cell neoplasms. Bayesian models were used as sensitivity analyses. Seventy-five RCTs including 270,471 participants were eligible. Dulaglutide was associated with a significantly increased risk of overall hematologic malignancy (RR = 2.17, 95% CIs = 1.14–4.17). In contrast, tirzepatide (RR = 0.22, 95% CIs = 0.06–0.78) and linagliptin (RR = 0.51, 95% CIs = 0.27–0.95) were linked to a reduced overall risk. In histopathology-specific analyses, tirzepatide showed a significant protective association against non-Hodgkin’s lymphoma, whereas no agent demonstrated clear signals for leukemia or myeloma. In this histopathology-focused NMA, dulaglutide emerged as the only agent with a significantly elevated overall hematologic malignancy risk, whereas tirzepatide and linagliptin exhibited protective profiles. The lymphoma-specific benefit observed for tirzepatide underscores the value of histologic subclassification when evaluating oncologic safety of antidiabetic therapies and calls for targeted mechanistic and long-term outcome studies. TRIAL REGISTRATION: PROSPERO CRD420251151419. The study protocol was approved by the Institutional Review Board of the Tri-Service General Hospital, National Defense Medical University (TSGHIRB E202516007).

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BackgroundSodium-glucose cotransporter (SGLT) 2 inhibitors attenuate fasting glomerular hyperfiltration in people with type 2 diabetes (T2D). However, SGLT2-inhibition increases glucagon levels, which facilitate postprandial hyperfiltration. The impact of SGLT2 inhibition on protein-related hyperfiltration and postprandial (intra) kidney haemodynamic function is unclear. Moreover, the interaction with dipeptidyl-peptidase (DPP)-4 inhibitors, known to reduce glucagon levels and to affect meal-related factors modulating GFR, is unknown.AimsWe aimed to assess the effects of empagliflozin and linagliptin in mono- and combination therapy compared to the initiation and intensification of SU-derivative gliclazide treatment on fasting and postprandial kidney haemodynamic function.Materials and methodsWe compared three 16-week glucose-lowering strategies added to ongoing metformin monotherapy: (1) EMPA-LINA: 8-week empagliflozin 10 mg QD (EMPA0-8w) followed by the addition of 8-week linagliptin 5 mg QD (LINA8-16w); (2) LINA-EMPA: 8-week linagliptin (LINA0-8w) followed by the addition of 8-week empagliflozin (EMPA8-16w) versus (3) GLIC-GLIC: 8-week gliclazide 30 mg QD (GLIC0-8w) followed by the addition of 8-week gliclazide 30 mg (GLIC8-16w). We studied (intra) kidney haemodynamic interactions of this combination using iohexol and PAH clearance techniques to assess measured glomerular filtration rate (mGFR) and effective renal plasma flow (ERPF).ResultsWe studied n = 61 overweight people with T2D (HbA1c 62 + 11 mmol/mol, eGFR 89 [78-100] mL/min/1.73 m2 and urinary albumin-creatinine-ratio 1.0 [0.4-1.9] mg/mmol). In the fasting state, EMPA0-8w (-13.2; -21.3 to -5.1 mL/min) but not LINA0-8w reduced within-group mGFR. EMPA8-16w (-10.2; -16.5 to -4.0 mL/min) but not LINA8-16w reduced within-group mGFR. Following a proteinload, EMPA0-8w (-11.4; -20.2 to -2.6 mL/min) and EMPA8-16w (-16.2; -22.9 to -9.4 mL/min) but not LINA0-8w or LINA8-16w reduced within-group mGFR. Versus the comparatorarm, fasting mGFR EMPA0-8w, EMPA8-16w and EMPA-LINA and postprandial mGFR EMPA8-16w and LINA-EMPA, were significantly reduced. mGFR reductions resulted from intrakidney efferent vasodilation rather than afferent vasoconstriction.ConclusionIn T2D people without CKD, the favourable kidney haemodynamic effects of empagliflozin persist in the postprandial state and are irrespective of concurrent use of linagliptin.

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