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Cardiovascular safety of linagliptin compared with other oral glucose-lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care.

ABSTRACT: AIM:To evaluate the safety of linagliptin versus other glucose-lowering medications in a multi-year monitoring programme using insurance claims data. METHODS:In two commercial US claims databases, we identified three pairwise 1:1 propensity-score (PS)-matched cohorts of patients with type 2 diabetes (T2D) aged ?18?years initiating linagliptin or a comparator (other dipeptidyl peptidase-4 [DPP-4] inhibitors [n?=?31 492 pairs], pioglitazone [n?=?23 316 pairs], or second-generation sulphonylureas [n?=?19 731 pairs]) between May 2011 and December 2015. The primary endpoint was the risk of a composite cardiovascular (CV) outcome (hospitalization for myocardial infarction, stroke, unstable angina, or coronary revascularization). We estimated pooled hazard ratios (HRs) and 95% confidence intervals (CIs), controlling for >100 baseline characteristics. RESULTS:Patient characteristics were well balanced after PS-matching. The mean age was 55?years and mean follow-up was 0.8 years. Linagliptin conferred a similar risk of the composite CV outcome compared to other DPP-4 inhibitors (HR 0.91, 95% CI 0.79-1.05) and pioglitazone (HR 0.98, 95% CI 0.84-1.15), and showed a reduced risk of CV outcomes compared to second-generation sulphonylureas (HR 0.76, 95% CI 0.64--0.92). Key findings were signalled at the first interim analysis in June 2013 and solidified during ongoing monitoring until 2015. CONCLUSION:Analyses from a large monitoring programme in routine care of patients with T2D, showed that linagliptin had similar CV safety compared to other DPP-4 inhibitors and pioglitazone, and a reduced CV risk compared to sulphonylureas.

SUBMITTER: Patorno E

PROVIDER: S-EPMC6785989 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Cardiovascular safety of linagliptin compared with other oral glucose-lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care.

Patorno Elisabetta E Gopalakrishnan Chandrasekar C Brodovicz Kimberly G KG Meyers Andrea A Bartels Dorothee B DB Liu Jun J Kulldorff Martin M Schneeweiss Sebastian S

Diabetes, obesity & metabolism 20190501 8

<h4>Aim</h4>To evaluate the safety of linagliptin versus other glucose-lowering medications in a multi-year monitoring programme using insurance claims data.<h4>Methods</h4>In two commercial US claims databases, we identified three pairwise 1:1 propensity-score (PS)-matched cohorts of patients with type 2 diabetes (T2D) aged ≥18 years initiating linagliptin or a comparator (other dipeptidyl peptidase-4 [DPP-4] inhibitors [n = 31 492 pairs], pioglitazone [n = 23 316 pairs], or second-generation s ...[more]

PMID: 30941884

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Project description:Type 2 diabetes mellitus is an epidemic in Asia, yet clinical trials of glucose-lowering therapies often enroll predominantly Western populations. We explored the initial combination of metformin and linagliptin, a dipeptidyl peptidase-4 inhibitor, in newly diagnosed type 2 diabetes mellitus patients in Asia with marked hyperglycemia.This was a post-hoc subgroup analysis of a multinational, parallel-group clinical trial in which 316 newly diagnosed type 2 diabetes mellitus patients with glycated hemoglobin A1c (HbA1c) 8.5-12.0% were randomized to double-blind oral treatment with linagliptin/metformin or linagliptin monotherapy. The primary end-point was the change from baseline in HbA1c at week 24. We evaluated data for the 125 participants from Asian countries.After 24 weeks, the mean ± standard error reduction from baseline in HbA1c (mean 10.0%) was -2.99 ± 0.18% with linagliptin/metformin and -1.84 ± 0.18% with linagliptin; a treatment difference of -1.15% (95% confidence interval -1.65 to -0.66, P < 0.0001). HbA1c <7.0% was achieved by 60% of participants receiving linagliptin/metformin. The mean bodyweight change after 24 weeks was -0.45 ± 0.41 kg and 1.33 ± 0.45 kg in the linagliptin/metformin and linagliptin groups, respectively (treatment difference -1.78 kg [95% confidence interval -2.99 to -0.57, P = 0.0043]). Drug-related adverse events occurred in 9.7% of participants receiving linagliptin/metformin and 4.8% of those receiving linagliptin. Hypoglycemia occurred in 6.5% and 4.8% of the linagliptin/metformin and linagliptin groups, respectively, with no severe episodes. Gastrointestinal disorders occurred in 12.9% and 12.7% of the linagliptin/metformin and linagliptin groups, respectively, with no associated treatment discontinuations.In people from Asia with newly diagnosed type 2 diabetes mellitus and marked hyperglycemia, the initial combination of linagliptin and metformin substantially improved glycemic control without weight gain and with infrequent hypoglycemia. Initial oral combination therapy might be a viable treatment for such individuals.

Project description:IntroductionResearch has shown that glycemic control is associated with lower rates of microvascular and long-term cardiovascular complications. In the analyses reported here, we examined treatment failure on oral glucose-lowering agents (GLAs), defined as having sustained hemoglobin A1c (HbA1c) ≥ 7%.MethodsThis study utilized the IBM® MarketScan® Claims and Laboratory Data from 1 January 2012 through 30 June 2018. Adults with type 2 diabetes (T2D) were classified based upon the maximum number of classes of GLAs prescribed per day during the time period from 1 July 2012 through 31 December 2012. Patients were followed for 5.5 years in order to examine time to failure on oral GLAs, defined based upon receipt of ≥ 2 consecutive HbA1c results ≥ 7%. Multivariable analyses employing a Cox proportional hazards model were used to examine time to failure overall and based upon the number of index classes of oral GLAs prescribed. For patients who had sustained HbA1c above the threshold, multivariable analyses examined the duration of time that HbA1c remained above the threshold (i.e, glycemic burden) and whether or not an additional oral or injectable class of GLA was added to the patient treatment regimen (i.e., clinical inertia).ResultsA total of 4156 patients were included in the study, of whom 16% were identified with sustained HbA1c ≥ 7% after 365 days (1 year) and 36% after 730 days (2 years), with half of all patients having sustained HbA1c above target after 1102 days (3 years). There was a statistically significant difference in time to having sustained HbA1c above target based upon index classes of therapy, with patients treated with more GLAs being quicker to have HbA1c above target (P < 0.0001). Among those patients who were found to have sustained HbA1c ≥ 7%, the average number of days in the post-period that HbA1c remained above target was 1026 (2.8 years). Only 36% of patients with sustained HbA1c above target added a GLA to their treatment regimen and, for patients who did add such a therapy, the average duration from identification of HbA1c above target until treatment intensification was 401 days (1.1 years). Multivariable analyses revealed that, among those with sustained HbA1c ≥ 7%, treatment with more classes of oral GLAs was associated with a significantly higher glycemic burden and significantly lower odds of clinical inertia.ConclusionThese results indicate that for many patients treated with oral GLAs, glycemic control is not consistently achieved. For patients with above-target HbA1c , the results indicate a relatively large glycemic burden and clinical inertia towards treatment intensification. The findings illustrate some limitations associated with treatment of T2D with oral GLAs.

Project description:ObjectivesTo evaluate the extent to which patients with type 2 diabetes discontinue metformin therapy when initiating second-line treatment and factors associated with metformin discontinuation, using baseline data from the DISCOVER study programme.DesignDISCOVER is a 3-year, prospective, observational study programme including data from 38 countries across 6 continents from 2014 to 2019.SettingPrimary and secondary healthcare centres, hospitals and specialist diabetes centres in both urban and rural locations.ParticipantsA total of 15 992 patients with type 2 diabetes initiating second-line glucose-lowering therapy.Primary and secondary outcome measuresThe proportion of patients who discontinued metformin as a second-line therapy and the factors associated with this treatment change.ResultsOf the 14 668 patients (from 37 countries) with valid treatment data, 11 837 (80.7%) received metformin as first-line glucose-lowering therapy; 8488 (71.7%) received metformin monotherapy and 3349 (28.3%) received metformin as part of a combination therapy. Overall, treatment with metformin was discontinued in 15.1% (1782) of patients who received first-line metformin (14.1% (1194) and 17.6% (588) in those who received metformin as monotherapy and as part of a combination, respectively); this proportion varied across regions from 6.9% (54) in Africa to 20.6% (628) in South-East Asia. On metformin discontinuation, 73.6% (1311) of patients received a non-insulin monotherapy at second line. Factors associated with an increased odds of metformin discontinuation were older age (≥75 years) and having a history of chronic kidney disease. The probability of metformin monotherapy discontinuation was lower in patients from Africa than in those from Europe.ConclusionsA substantial number of patients discontinued taking metformin when beginning second-line therapy. Most of these patients subsequently received a non-insulin monotherapy at second line, in contradiction to international guidelines and potentially leaving them at an increased risk of hyperglycaemia and associated adverse outcomes.Trial registration numbersNCT02322762 and NCT02226822.

Dataset Information

Cardiovascular safety of linagliptin compared with other oral glucose-lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care.

Publications

Cardiovascular safety of linagliptin compared with other oral glucose-lowering agents in patients with type 2 diabetes: A sequential monitoring programme in routine care.

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