Diabetes Therapy最新文献

{"title":"Integrated Evidence from VigiBase and Clinical Trials: A Comprehensive Pharmacovigilance Analysis of Seven Glucagon-Like Peptide 1 Receptor Agonists (GLP-1 RAs).","authors":"Jiaxun Li, Jizhou Liang, Wei Zhang, Jia He, Xiaofei Ye","doi":"10.1007/s13300-026-01872-6","DOIUrl":"10.1007/s13300-026-01872-6","url":null,"abstract":"<p><strong>Introduction: </strong>Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are key therapies for type 2 diabetes and obesity, regulating blood glucose by mimicking endogenous GLP-1. Despite efficacy, GLP-1 RAs are associated with adverse reactions across multiple organ systems. To address the gap in class-wide comparative safety analyses beyond previous studies limited to single drugs or organ systems, this study systematically evaluated adverse events for all approved GLP-1 RAs to identify hidden risks and support clinical decision-making.</p><p><strong>Methods: </strong>We conducted a disproportionality analysis using the World Health Organization pharmacovigilance database (VigiBase) data up to January 2025. Reporting odds ratio (ROR) and information component (IC) were calculated for seven GLP-1 RAs. Signals were considered significant when ROR₀₂₅ > 1 and IC₀₂₅ > 0. Subgroup analyses were stratified by gender and age. We aimed to synthesize and analyze existing randomized controlled trials (RCT) to validate VigiBase mining results.</p><p><strong>Results: </strong>Among 348,649 reports, gastrointestinal disorders were the most frequent System Organ Class. Notable signals included tirzepatide with \"abdominal pain\" (ROR₀₂₅ = 53.54), liraglutide with \"drug ineffective\" (ROR₀₂₅ = 31.14) and \"pancreatitis\" (ROR₀₂₅ = 4.24), exenatide with \"injection site pain\" (ROR₀₂₅ = 70.14), and albiglutide with \"device use error\" (ROR₀₂₅ = 1424.33). Male patients and younger adults (18-44 years) generally showed higher positive reporting rates.</p><p><strong>Conclusions: </strong>This study provides a comprehensive safety comparison across all seven approved GLP-1 RAs, confirming known risks and revealing drug-specific signals-such as injection-related issues and paradoxical hyperglycemia. These findings aid personalized treatment strategies and post-marketing surveillance.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"853-872"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of SGLT2 Inhibitors on Clinical Outcomes in Patients with Diabetes Mellitus Following Heart Transplantation: A Meta-analysis.","authors":"Hong Wang, Xiaoya Xie, Guoping Gong, Liuqiang Huang, Zhangui Tang","doi":"10.1007/s13300-026-01866-4","DOIUrl":"10.1007/s13300-026-01866-4","url":null,"abstract":"<p><strong>Introduction: </strong>In this new era, heart transplantation (HT) is rapidly gaining popularity worldwide. Patients with end-stage heart disease are often candidates for HT. However, studies have shown that more than 30% of patients who undergo HT have pre-existing diabetes mellitus (DM), which is associated with a higher risk of graft failure and death. In this analysis, we aimed to assess the impact of sodium-glucose co-transporter 2 (SGLT2) inhibitors on clinical outcomes in patients with DM following HT.</p><p><strong>Methods: </strong>Online databases were searched for relevant publications. The statistical analysis was performed using the RevMan software version 5.4. The clinical outcomes included rejection post-HT, mortality, sepsis, weight reduction, change in body mass index (BMI), change in serum creatinine level, glomerular filtration rate (eGFR), and improvement in glycated hemoglobin (HbA1c). For dichotomous data, risk ratios (RR) with 95% confidence intervals (CI) were used to summarize the analysis. However, for continuous data, weight mean difference (WMD) with 95% CI was used.</p><p><strong>Results: </strong>Eight studies with a total number of 2755 participants were included in this analysis. Our current results showed that rejection risk post HT was significantly lower in the SGLT2 inhibitor group (RR: 0.85, 95% CI: 0.78-0.93; P = 0.0001). The mortality risk was not significantly different (RR: 0.64, 95% CI: 0.32-1.29; P = 0.21). Similarly, sepsis following HT was similar in both groups (RR: 1.62, 95% CI: 0.13-20.11; P = 0.71). No significant differences were observed in weight reduction, BMI, change in serum creatinine level, change in eGFR, or improvement in HbA1c following HT.</p><p><strong>Conclusions: </strong>In participants with DM following HT, SGLT2 inhibitors significantly reduced rejection post transplantation. However, its impact on other important clinical outcomes, including mortality, should be further assessed with more data in future studies.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"839-852"},"PeriodicalIF":4.2,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13253890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness and Safety of Escalating Once-Weekly Semaglutide from 0.5 to 1.0 mg in Type 2 Diabetes.","authors":"Genki Sato, Hiroshi Uchino, Kota Takuma, Manabu Saito, Ayako Fuchigami, Yoko Iwata, Fukumi Yoshikawa, Takahisa Hirose","doi":"10.1007/s13300-026-01864-6","DOIUrl":"10.1007/s13300-026-01864-6","url":null,"abstract":"<p><strong>Introduction: </strong>Real-world data on escalation of once-weekly semaglutide from 0.5 to 1.0 mg remain limited. Therefore, we aimed to evaluate the effectiveness and safety of this dose escalation in routine clinical practice.</p><p><strong>Methods: </strong>This was a single-center, retrospective cohort study involving adults with type 2 diabetes who received an escalated once-weekly semaglutide dose from 0.5 to 1.0 mg in routine clinical care. The primary outcome was within-patient change in glycated hemoglobin (HbA1c) level 24 weeks after the initial prescription of 1-mg semaglutide. Secondary outcomes included changes in metabolic parameters and the incidence of newly documented adverse events after escalation to 1.0 mg. Efficacy was analyzed in a prespecified on-treatment set, and safety was assessed in an all-exposed set.</p><p><strong>Results: </strong>In the efficacy set (n = 126), the HbA1c level decreased by 0.40% ± 0.70% and body weight by 2.2 ± 2.7 kg at week 24 (both p < 0.01). Additionally, reductions were observed in alanine aminotransferase and γ-glutamyl transpeptidase levels, total number of concomitant glucose-lowering agents, and total daily insulin dose. In the safety set (n = 128), gastrointestinal adverse events were the most frequent (20.3%), particularly nausea (14.1%). Dose reduction was required in 12.5% of patients, mostly owing to gastrointestinal symptoms, and discontinuation for any reason occurred in 5.5%; only one patient (0.8%) discontinued treatment because of an adverse event. No serious drug-related adverse events were recorded.</p><p><strong>Conclusions: </strong>In this real-world cohort, escalation of once-weekly semaglutide dose to 1.0 mg was associated with additional reductions in HbA1c level and body weight, without serious adverse events. Although causal incremental benefit cannot be established because of the single-arm design without a 0.5-mg maintenance comparator, these findings may support clinical decision-making regarding dose intensification in patients experiencing suboptimal control with 0.5-mg semaglutide.</p><p><strong>Trial registration: </strong>UMIN Clinical Trials Registry (UMIN-CTR), UMIN000059813, retrospectively registered on November 18, 2025.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"753-770"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147632872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucagon-Like Peptide-1 Receptor Agonists: Their Potential Role in Prediabetes.","authors":"Theodoros Panou, Evanthia Gouveri, Djordje S Popovic, Dimitrios Papazoglou, Nikolaos Papanas","doi":"10.1007/s13300-026-01865-5","DOIUrl":"10.1007/s13300-026-01865-5","url":null,"abstract":"<p><p>Prediabetes is a frequently occurring condition with increased risk of type 2 diabetes mellitus (T2DM) and cardiovascular disease. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are established antidiabetic agents, also used to treat obesity. There is limited, yet promising evidence on their use in prediabetes. T2DM was less frequent among subjects on liraglutide, semaglutide and tirzepatide compared with the control arm. Delayed progression to T2DM has also been observed. Furthermore, normoglycaemia was achieved for subjects on liraglutide (up to 66%), semaglutide (up to 81%) and tirzepatide (up to 93.3%). However, this effect was only partially sustained following drug withdrawal. GLP-1RAs have led to modest decreases in glycated haemoglobin (HbA_1c), fasting glucose, weight and fat mass loss, as well as increased insulin sensitivity and improved β-cell glucose-insulin dynamics. Decreased risk for atherosclerotic cardiovascular disease and heart failure was also demonstrated, mostly for subjects on tirzepatide. There is experimental evidence on improvements in liver dysfunction, pointing to potential benefits for metabolic dysfunction-associated steatotic liver disease (MASLD) in prediabetes. The safety profile was acceptable with mild-to-moderate gastrointestinal adverse effects being mostly reported. Future large randomised controlled trials are needed to ascertain the exact role of GLP-1RAs in prediabetes.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"641-669"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156392/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Comparative Safety of SGLT2 Versus DPP4 Inhibitors in Patients with Type 2 Diabetes: A Meta‑Analysis of Randomized Controlled Trials.","authors":"Yue Li, Jie Chen, Yuying Gao, Jun Zhang, Siqiong Deng, Hao Li, Xin Zhang, Rui Li","doi":"10.1007/s13300-026-01862-8","DOIUrl":"10.1007/s13300-026-01862-8","url":null,"abstract":"","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"711-713"},"PeriodicalIF":2.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147688758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparative Safety of SGLT2 Versus DPP4 Inhibitors in Patients with Type 2 Diabetes: A Meta-Analysis of Randomized Controlled Trials.","authors":"Yue Li, Jie Chen, Yuying Gao, Jun Zhang, Siqiong Deng, Hao Li, Xin Zhang, Rui Li","doi":"10.1007/s13300-025-01836-2","DOIUrl":"10.1007/s13300-025-01836-2","url":null,"abstract":"<p><strong>Introduction: </strong>Type 2 diabetes mellitus (T2DM) necessitates long-term pharmacological management, with drug safety now a pivotal factor in therapy selection. Sodium‒glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase 4 inhibitors (DPP4is) are widely prescribed oral antidiabetic agents; however, their comparative safety profiles remain under debate.</p><p><strong>Methods: </strong>A systematic search of PubMed, Embase, the Cochrane Library, and Web of Science was performed up to June 2, 2025. Forty-two randomized controlled trials (RCTs) that compared SGLT2is with DPP4is in adults with T2DM were included. Pooled risk ratios (RRs) with 95% confidence intervals (CIs) were calculated using Review Manager (RevMan) 5.3. Heterogeneity was assessed with I², and publication bias with funnel plots and Egger's test.</p><p><strong>Results: </strong>SGLT2is were associated with a higher overall risk of total adverse events (AEs) (RR 1.05, 95% CI 1.01-1.08). Infection-related risks included increased genital infections (RR 5.31, 95% CI 3.93-7.18) and urinary tract infections (UTIs) (RR 1.45, 95% CI 1.25-1.70), with no difference in upper respiratory tract infections (URTIs) (RR 0.78, 95% CI 0.61-1.02). For organ injury, a non-significant trend toward renal injury was noted (RR 1.83, 95% CI 0.92-3.67), with no difference in liver injury (RR 0.64, 95% CI 0.28-1.46) or fracture (RR 0.83, 95% CI 0.25-2.70). Severe outcomes-including hypoglycemia (RR 1.07, 95% CI 0.88-1.29), mortality (RR 1.48, 95% CI 0.59-3.71), diabetic ketoacidosis (DKA) (RR 2.99, 95% CI 0.31-28.45), and major adverse cardiovascular events (MACEs) (RR 1.21, 95% CI 0.35-4.19)-did not differ. Hypersensitivity risk was also comparable (RR 1.25, 95% CI 0.65-2.42).</p><p><strong>Conclusion: </strong>SGLT2is have an overall favorable safety profile but increase the risks of genitourinary infections and transient renal impairment. Risk stratification and monitoring are essential for high-risk individuals, for whom DPP4is may be safer. These findings provide robust RCT-based evidence to inform individualized treatment and guideline updates.</p><p><strong>Trial registration: </strong>This systematic review and meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 statement. The protocol was prospectively registered with the International Prospective Register of Systematic Reviews (PROSPERO; registration number CRD420251115623).</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"685-709"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156394/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146164647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety of Insulin Efsitora Versus Degludec in Adults with Type 2 Diabetes Who Are Insulin-Naïve: Japan Subgroup Analysis of QWINT-2.","authors":"Arihiro Kiyosue, Mariko Inoue, Yasushi Takita, Risa Nasu, Hirotaka Watada","doi":"10.1007/s13300-026-01860-w","DOIUrl":"10.1007/s13300-026-01860-w","url":null,"abstract":"<p><strong>Introduction: </strong>The phase 3 QWINT-2 study demonstrated that once-weekly insulin efsitora alfa (efsitora) was noninferior to once-daily insulin degludec (degludec) in reducing glycated hemoglobin (HbA1c) at week 52 when added to existing noninsulin glucose-lowering agents in adults with type 2 diabetes who were insulin-naïve. A Japan subgroup analysis of QWINT-2 using two dosing algorithms is presented here.</p><p><strong>Methods: </strong>Participants from Japan were randomized 1:1 to efsitora or degludec and followed one of two dosing algorithms: a general dosing algorithm or an optional alternative dosing algorithm available for participants anticipated to require less insulin, characterized by a body weight ≤ 60 kg or HbA1c level ≤ 7.5% at baseline. Assessments included changes in HbA1c and fasting blood glucose from weeks 0-52, time spent in target glucose range (TIR) from weeks 48-52, and hypoglycemia from weeks 0-52.</p><p><strong>Results: </strong>In total, 144 participants from Japan were included (efsitora, n = 71; degludec, n = 73). Demographic and baseline characteristics were generally balanced between treatment groups. From weeks 0-52, mean HbA1c decreased from 8.04% to 6.63% with efsitora and from 8.00% to 6.64% with degludec (estimated treatment difference, -0.01%). TIR was similar between efsitora and degludec from weeks 48-52. Rates of combined level 2 or 3 hypoglycemia were low overall (weeks 0-52) and during the initial dosing period (weeks 0-12). Level 3 hypoglycemia was not reported in any participants with efsitora and two participants with degludec. The incidence of adverse events was similar between efsitora and degludec. The efficacy and safety of efsitora were comparable with degludec using the general and alternative dosing algorithms in Japanese participants.</p><p><strong>Conclusions: </strong>Once-weekly efsitora was comparable to once-daily degludec in reducing HbA1c in Japanese participants who were insulin-naïve. The efficacy and safety of efsitora in Japanese participants were consistent with the overall QWINT-2 study population.</p><p><strong>Clinicaltrials: </strong></p><p><strong>Gov identifier: </strong>NCT05362058.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":"17 5","pages":"771-785"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13199571/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005030","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ten-Year Trends in Healthcare Use and Costs for People Living with Diabetes in France: Results from the Epicodiab Study Based on National Claims Data.","authors":"Michael Joubert, Pierre Serusclat, Emilie Casarotto, Oriane Bretin, Barbara Roux, Pascaline Rabiéga, Yolaine Rabat, Cécile Berteau, Antoine Pouyet, Guy Fagherazzi","doi":"10.1007/s13300-026-01850-y","DOIUrl":"10.1007/s13300-026-01850-y","url":null,"abstract":"<p><strong>Introduction: </strong>Diabetes remains a global public health concern, with increased prevalence and a significant economic burden. Yet, most studies do not differentiate between type 1 (T1D) and type 2 diabetes (T2D), despite distinct clinical trajectories and care needs. This study aimed to provide up-to-date data on healthcare use and diabetes care-related costs in France from 2011 to 2019 by type of diabetes.</p><p><strong>Methods: </strong>A 10-year retrospective study was conducted on adults identified with T1D and T2D between 1 January 2010, and 31 December 2019, in a 1/10th sample of the French nationwide claims database (SNDS, Système National des Données de Santé). In the hospital database, reimbursement data are available only from 2011, so resource use and cost analyses were conducted starting from 2011 to 2019 in this present study. Diabetes was identified through hospital diagnoses, specific treatments, and/or long-term conditions. A machine-learning algorithm was specifically developed through a linkage between SNDS data and primary data from a network of French general practitioners to better predict the type of diabetes.</p><p><strong>Results: </strong>In 2019, among the 290,486 treated individuals, 12,102 (4.2%) had T1D, 62,479 (21.5%) had insulin-treated type 2 diabetes (T2Di), and 215,905 (74.3%) had noninsulin-treated type 2 diabetes (T2Dni). Average total reimbursed costs per individual varied significantly by diabetes group: €10,033 (T1D), €13,424 (T2Di), and €5091 (T2Dni), primarily owing to primary care settings (63.6% to 71.8% of the total cost). Between 2011 and 2019, total reimbursement costs increased (+ 9.6% for T1D, + 29.8% for T2Di, and + 13.8% for T2Dni), while average cost per individual decreased (-9.6% for T1D, -7.7% for T2Di, and -1.0% for T2Dni).</p><p><strong>Conclusions: </strong>As its prevalence continues to rise, the economic burden of diabetes also grows overall, despite the reduction in individual costs.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"735-752"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147510401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fixed-Dose Combination Therapy as a Strategy to Improve Antidiabetic Medication Adherence in People with Type 2 Diabetes: A Narrative Review.","authors":"Patrick J Highton, Mark P Funnell, Kamlesh Khunti","doi":"10.1007/s13300-026-01863-7","DOIUrl":"10.1007/s13300-026-01863-7","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a metabolic condition associated with increased morbidity, mortality and healthcare costs, with poor medication adherence to antidiabetic medications being a major barrier to optimal risk-factor control. Treatment complexity, due to polypharmacy and burdensome dosing regimens, is a key contributor to medication non-adherence in people with T2DM. Fixed-dose combination (FDC) therapy, in which two or more drugs are co-formulated into a single dosage, has emerged as a key strategy to reduce treatment burden, simplify dosing and potentially improve adherence in T2DM. This narrative review evaluates the evidence for FDC therapy as a means of improving medication adherence in people with T2DM. We summarise the development of FDCs, commonly used antidiabetic regimens, patient-reported benefits and their role in clinical practice. Evidence from randomised controlled trials (RCTs) assessing medication adherence is limited, but observational studies consistently demonstrate improved adherence among patients prescribed FDCs compared with free-equivalent combination regimens. Systematic reviews and meta-analyses support these findings, showing that FDCs attenuate the decline in medication adherence observed when transitioning from monotherapy to combination therapy. Additional benefits of FDC therapy include greater treatment satisfaction, potential cost-effectiveness and safety profiles comparable to their individual components. However, challenges associated with FDC therapy remain, including limited dosing flexibility, difficulties in titration and a paucity of long-term adherence data. Further research, particularly RCTs comparing FDCs with equivalent separate combinations and long-term follow-up data, are needed to confirm these benefits and inform clinical guidelines. Overall, FDC therapy is beneficial for simplifying diabetes treatment and improving medication adherence in T2DM.</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"627-640"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644060","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirzepatide as an Add-on for Participants with Inadequate Glycemic Control Using Basal Insulin: Pooled Subgroup Analysis of SURPASS-5 and -6.","authors":"Harpreet S Bajaj, Liana K Billings, Palash Sharma, Joshua A Levine, Angel Rodriguez, Hiren Patel","doi":"10.1007/s13300-026-01859-3","DOIUrl":"10.1007/s13300-026-01859-3","url":null,"abstract":"<p><strong>Introduction: </strong>This study aimed to assess the efficacy and hypoglycemia safety of tirzepatide as an add-on to basal insulin in people with inadequate glycemic control, across subgroups of baseline age, type 2 diabetes (T2D) duration, HbA1c, and basal insulin dosage using pooled data from the SURPASS-5 and -6 studies.</p><p><strong>Methods: </strong>This exploratory post hoc analysis compared data from 1072 participants treated with tirzepatide as an add-on to basal insulin in SURPASS-5 and SURPASS-6. In SURPASS-5, tirzepatide was compared against placebo, while in SURPASS-6, it was compared with insulin lispro. Insulins were titrated to the target in both trials. Subgroups were divided by baseline HbA1c (≤ 8.5% and > 8.5%), age (< 65 years and ≥ 65 years), duration of T2D (< 10 years and ≥ 10 years), and insulin glargine dose (< 50 IU/day and ≥ 50 IU/day).</p><p><strong>Results: </strong>At the primary endpoint, tirzepatide added to basal insulin glargine was associated with significant reductions in HbA1c, fasting serum glucose, and insulin glargine dose across all subgroups (P < 0.001), with no significant heterogeneity (all interaction P values > 0.1). Clinically significant hypoglycemia incidence rates were highest in younger participants with a baseline HbA1c above 8.5% and duration of T2D ≥ 10 years.</p><p><strong>Conclusions: </strong>In this study, tirzepatide combined with basal insulin glargine was associated with reductions in HbA1c, fasting serum glucose, and insulin glargine dose from baseline, with a low incidence of hypoglycemia, regardless of baseline age, HbA1c, duration of T2D, or basal insulin dose.</p><p><strong>Trial registration: </strong>Trials were registered at ClinicalTrials.gov under the identifiers NCT04039503 (SURPASS-5) and NCT04537923 (SURPASS-6).</p>","PeriodicalId":11192,"journal":{"name":"Diabetes Therapy","volume":" ","pages":"787-797"},"PeriodicalIF":4.2,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13156352/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147644117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}