Association between dipeptidyl peptidase‐4 inhibitors and urinary tract infection in elderly patients: A retrospective cohort study

Imatoh, Takuya; Nishi, Takumi; Yasui, Midori; Maeda, Toshiki; Sai, Kimie; Saito, Yoshiro; Une, Hiroshi; Babazono, Akira

doi:10.1002/pds.4560

Cited by 9 publications

(5 citation statements)

References 28 publications

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“…Symptomatic hypoglycemia, pancreatitis (acute or chronic), skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major AEs. [18][19][20][21][22] Microvascular and macrovascular complications were also collected. AE terms were referred to MedDRA V. 15 Clinical care/Education/Nutrition included the levels of hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin, and urinary albumin.…”

Section: Discussionmentioning

confidence: 99%

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Ueki

Tanizawa

Nakamura

et al. 2021

BMJ Open Diab Res Care

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IntroductionGiven an increasing use of dipeptidyl peptidase-4 (DPP-4) inhibitors to treat patients with type 2 diabetes mellitus in the real-world setting, we conducted a prospective observational study (Japan-based Clinical Research Network for Diabetes Registry: J-BRAND Registry) to elucidate the safety and efficacy profile of long-term usage of alogliptin.Research design and methodsWe registered 5969 patients from April 2012 through September 2014, who started receiving alogliptin (group A) or other classes of oral hypoglycemic agents (OHAs; group B), and were followed for 3 years at 239 sites nationwide. Safety was the primary outcome. Symptomatic hypoglycemia, pancreatitis, skin disorders of non-extrinsic origin, severe infections, and cancer were collected as major adverse events (AEs). Efficacy assessment was the secondary outcome and included changes in hemoglobin A1c (HbA1c), fasting blood glucose, fasting insulin and urinary albumin.ResultsOf the registered, 5150 (group A: 3395 and group B: 1755) and 5096 (3358 and 1738) were included for safety and efficacy analysis, respectively. Group A patients mostly (>90%) continued to use alogliptin. In group B, biguanides were the primary agents, while DPP-4 inhibitors were added in up to ~36% of patients. The overall incidence of AEs was similar between the two groups (42.7% vs 42.2%). Kaplan-Meier analysis revealed the incidence of cancer was significantly higher in group A than in group B (7.4% vs 4.8%, p=0.040), while no significant incidence difference was observed in the individual cancer. Multivariate Cox regression analysis revealed that the imbalanced patient distribution (more elderly patients in group A than in group B), but not alogliptin usage per se, contributed to cancer development. The incidence of other major AE categories was with no between-group difference. Between-group difference was not detected, either, in the incidence of microvascular and macrovascular complications. HbA1c and fasting glucose decreased significantly at the 0.5-year visit and nearly plateaued thereafter in both groups.ConclusionsAlogliptin as a representative of DPP-4 inhibitors was safe and durably efficacious when used alone or with other OHAs for patients with type 2 diabetes in the real world setting.

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Section: Discussionmentioning

confidence: 99%

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Ueki

Tanizawa

Nakamura

et al. 2021

BMJ Open Diab Res Care

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“…Even though UTI is not a known adverse effect of DPP4i, there is a single study that reported an increased risk of UTI with the use of DPP4i when compared with sulfonylureas. 28 We also observed inverse associations between SGLT2is and anemias (D64). Meta-analyses of RCTs found that SGLT2i use increased hemoglobin levels in patients with diabetes and chronic kidney disease.…”

Section: Discussionmentioning

confidence: 57%

“…We cannot exclude the possibility that the lower rate of UTI hospitalization among SGLT2i users was due to adverse events following DPP4i use. Even though UTI is not a known adverse effect of DPP4i, there is a single study that reported an increased risk of UTI with the use of DPP4i when compared with sulfonylureas 28 …”

Section: Discussionmentioning

confidence: 99%

SGLT‐2 Inhibitor Use and Cause‐Specific Hospitalization Rates: An Outcome‐Wide Study to Identify Novel Associations of SGLT‐2 Inhibitors

Tan,

Morton,

Wood

et al. 2024

Clin Pharma and Therapeutics

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Sodium‐glucose co‐transporter 2 inhibitors (SGLT2is) have demonstrated multifaceted pharmacological effects. In addition to type 2 diabetes, they are now indicated for heart failure and chronic kidney disease. This study aimed to identify novel associations between SGLT2i use and health outcomes using real‐world data. Using linked data from a nationwide diabetes registry in Australia, we compared hospitalization rates in people living with type 2 diabetes commencing treatment with SGLT2i and dipeptidyl peptidase‐4 inhibitor (DPP4i) between December 1, 2013, and June 30, 2019. Cause‐specific hospitalizations were categorized across three hierarchies of diagnoses (first, first three, and first four digits of International Classification of Diseases, Tenth Version, Australian Modification codes). Incidence rate ratio (IRR) and 95% confidence interval (95% CI) for each cause‐specific hospitalization were estimated using negative binomial regression. In the first hierarchy, hospitalization rates were lower across most diagnosis groups among SGLT2i initiators (n = 99,569) compared with DPP4i initiators (n = 186,353). In the second and third hierarchies, there were lower hospitalization rates relating to infections, anemias, and obstructive airway diseases among SGLT2i initiators compared with DPP4i initiators. These included sepsis (IRR: 0.60, 95% CI: 0.51–0.72) anemia (IRR: 0.55, 95% CI: 0.46–0.66), and chronic obstructive pulmonary diseases (IRR: 0.52, 95% CI: 0.40–0.68), as well as for previously known associations (e.g., heart failure (IRR: 0.63, 95% CI: 0.56–0.70)). SGLT2is have previously uncharacterized associations on a range of important clinical outcomes; validation of these associations requires further study, some of which may suggest novel benefits or new indications for SGLT2is.

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“…Sodium-glucose cotransporter 2 (SGLT2) mediates approximately 80–90% of renal glucose reabsorption under normal physiologic conditions, and SGLT2i can reduce 30–50% of the filtered glucose load in T2DM patients by increasing urinary glucose excretion [ 41 ]. However, the Food and Drug Administration (FDA) issued safety warnings for UTIs which may represent a leading cause of sepsis and are potentially life-threatening [ 42 , 43 ]. We conducted a meta-analysis to evaluate the benefit on the cardiovascular system and the potential risk of infection of SGLT2i in T2DM patients compared to metformin.…”

Section: Discussionmentioning

confidence: 99%

The Cardiovascular Benefits and Infections Risk of SGLT2i versus Metformin in Type 2 Diabetes: A Systemic Review and Meta-Analysis

Zhang

et al. 2022

Metabolites

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Sodium-glucose cotransporter 2 inhibitors (SGLT2i) and metformin are both widely accepted anti-hyperglycemic agents. However, there is still no systematic review evaluating the cardiovascular benefits and risk of infections of SGLT2i versus metformin. To make that clear, we designed this study. Public databases, including the Cochrane library database, PubMed, and Embase were searched for randomized clinical trials (RCTs) fitting the inclusion criteria. Two reviewers extracted the data and appraised the study quality independently. Thirteen RCTs enrolling 4189 patients were eligible for this analysis. Our results showed that compared with metformin, SGLT2i increased the risk of genitourinary tract infections (p < 0.00001). Further subgroup analysis suggested that the occurrence of urinary tract infections (UTI) was not statistically significant (p = 0.18), but the incidence of reproductive tract infections (RTI) was significantly increased in patients in the SGLT2i group compared with that in the metformin group (p < 0.00001). In addition, SGLT2i markedly decreased the levels of cardiovascular risk factor, including body weight, blood pressure, and triglyceride level, and significantly increased the HDL-cholesterol level (p < 0.00001) in patients versus that of metformin. For type 2 diabetes patients with obesity, SGLT2i was associated with more significant reductions in weight and blood pressure compared to metformin without an increased risk of genitourinary infections, and the reduction in fasting plasma glucose was superior in the SGLT2i group; the decrease in HbA1c was similar in both groups. Additionally, no significant publication bias was seen. Based on these findings, SGLT2i provided the similar antihyperglycemic effects, additional cardiovascular benefits, and a potential RTI risk compared with that of metformin. Our results indicate that SGLT2i is a good choice for those patients with metformin intolerance or resistance.

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Association between dipeptidyl peptidase‐4 inhibitors and urinary tract infection in elderly patients: A retrospective cohort study

Abstract: The long-term use of DPP-4 inhibitors by elderly patients, particularly male patients with prostatic hyperplasia, may increase the risk of UTI.

Cited by 9 publications

References 28 publications

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

Long-term safety and efficacy of alogliptin, a DPP-4 inhibitor, in patients with type 2 diabetes: a 3-year prospective, controlled, observational study (J-BRAND Registry)

SGLT‐2 Inhibitor Use and Cause‐Specific Hospitalization Rates: An Outcome‐Wide Study to Identify Novel Associations of SGLT‐2 Inhibitors

The Cardiovascular Benefits and Infections Risk of SGLT2i versus Metformin in Type 2 Diabetes: A Systemic Review and Meta-Analysis

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