Dataset Information

Evolving channeling in prescribing SGLT-2 inhibitors as first-line treatment for type 2 diabetes.

ABSTRACT:

Purpose

Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-line monotherapy.

Methods

Using claims data from two US commercial health insurance and Medicare, we identified patients with T2D aged ≥18 years (>65 years in Medicare) initiating first-line SGLT-2i or metformin from 2013 through 2019. Standardized differences (SDs) for patient characteristics were assessed during four consecutive calendar time blocks (T1:4/2013-12/2014; T2:1/2015-6/2016; T3:7/2016-12/2017; and T4:1/2018-12/2019). We also estimated the propensity score of receiving SGLT-2i versus metformin within each time block and evaluated time trends in model discrimination with c-statistics.

Results

We identified 9113 initiators of first-line SGLT-2i and 810 348 initiators of first-line metformin. During T1, SGLT-2i initiators were younger (SD = -0.24) and less likely to have seen cardiologists (-0.07) with a similar prevalence of CVD (0.04) compared with metformin. During T4, patients were more balanced for age (-0.01). Cardiologist visits (0.08) and CVD (0.25) became more prevalent among SGLT-2i initiators.

Conclusions

When comparing initiators of first-line SGLT-2i versus metformin, imbalances in patient characteristics evolved from 2013 through 2019, particularly channeling SGLT-2i to individuals at high cardiovascular risk. Evolving channeling in prescribing first-line SGLT-2i should be expected and accounted for in non-randomized comparative effectiveness research.

SUBMITTER: Shin H

PROVIDER: S-EPMC8989653 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

Evolving channeling in prescribing SGLT-2 inhibitors as first-line treatment for type 2 diabetes.

Shin HoJin H Schneeweiss Sebastian S Glynn Robert J RJ Patorno Elisabetta E

Pharmacoepidemiology and drug safety 20220117 5

<h4>Purpose</h4>Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are increasingly being considered as first-line treatment for type 2 diabetes (T2D). The benefits of SGLT-2i from cardiovascular outcome trials may lead to preferential prescribing of SGLT-2i to patients at high cardiovascular risk, possibly causing confounding in non-randomized studies of SGLT-2i as first-line treatment. We assessed evolving imbalances in characteristics of patients starting SGLT-2i versus metformin as first-li ...[more]

PMID: 34985178

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Project description:IntroductionFor people with type 2 diabetes (T2DM) inadequately controlled with oral antidiabetic drugs (OADs), evidence from both randomized controlled trials (RCTs) and real-world studies has demonstrated that treatment intensification with liraglutide offers effective glycemic control, weight reduction, and a lower risk of hypoglycemia compared to treatment intensification with insulin or additional OADs. Sodium glucose cotransporter 2 (SGLT-2) inhibitors are a new class of OADs that have also been shown to be effective in T2DM patients inadequately controlled with OADs. Currently there are no head-to-head RCTs comparing these to liraglutide.MethodsWe aimed to evaluate the relative efficacy, using network meta-analysis (NMA), of treatment intensification with liraglutide and SGLT-2 inhibitors people with T2DM who have been treated with metformin (alone or in combination with SU, DPP-4, and TZD). We performed a systematic literature review to identify relevant RCTs comparing liraglutide (1.2 and 1.8 mg), canagliflozin (100 and 300 mg), empagliflozin (10 and 25 mg), or dapagliflozin (5 and 10 mg) to placebo. To strengthen the indirect evidence base, we also included non-placebo RCTs where sitagliptin (100 mg) was the active comparator. Bayesian NMA was performed on the following outcomes to assess the relative efficacy and safety of interventions: reduction (change) in HbA1c, weight, and fasting plasma glucose (FPG) as well as proportion reaching target HbA1c (<7%), and risk of hypoglycemia. Doses for each intervention were considered separately.ResultsA total of 16 RCTs were identified. All trials were similar with respect to important baseline characteristics and study design. Both doses of liraglutide were generally statistically significantly superior to the SGLT-2s with respect to change from baseline in HbA1c and FPG as well as odds of reaching target HbA1c <7%. For weight, canagliflozin 300 mg was superior to liraglutide 1.2 mg, and SGLT-2s were generally associated with larger change from baseline in weight. For risk of major or minor hypoglycemia, no differences were found between treatments.ConclusionsCompared to SGLT-2 inhibitors, liraglutide offers improvement in HbA1c and FPG. Reductions in weight are likely comparable between liraglutide and SGLT-2s. Liraglutide did not differ from SGLT-2s in terms of risk of hypoglycemia. Given the lack of head-to-head evidence, this analysis provides valuable insight into the comparative outcomes of liraglutide versus SGLT-2 inhibitors.

Project description:BackgroundMajor prospective randomized clinical safety trials have demonstrated beneficial effects of treatment with glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i) in people with type 2 diabetes and elevated cardiovascular risk, and recent clinical treatment guidelines therefore promote early use of these classes of pharmacological agents. In this Swedish nationwide observational study, we compared cardiorenal outcomes and safety of new treatment with GLP-1RA and SGLT-2i in people with type 2 diabetes.MethodsWe linked data from national Swedish databases to capture patient characteristics and outcomes and used propensity-score based matching to account for differences between the two groups. The treatments were compared using Cox regression models.ResultsWe identified 9648 participants starting GLP-1RA and 12,097 starting SGLT-2i with median follow-up times 1.7 and 1.1 years, respectively. The proportion of patients with a history of MACE were 15.8%, and 17.0% in patients treated with GLP-1RA and SGLT-2i, respectively. The mean age was 61 years with 7.6 years duration of diabetes. Mean HbA1c were 8.3% (67.6 mmol/mol) and 8.3% (67.2 mmol/mol), and mean BMI 33.3 and 32.5 kg/m2 in patients treated with GLP-1RA or SGLT-2i, respectively. The cumulative mortality risk was non-significantly lower in the group treated with SGLT-2i, HR 0.78 (95% CI 0.61-1.01), as were incident heart failure outcomes, but the risks of cardiovascular or renal outcomes did not differ. The risks of stroke and peripheral artery disease were higher in the SGLT-2i group relative to GLP-1RA, with HR 1.44 (95% CI 0.99-2.08) and 1.68 (95% CI 1.04-2.72), respectively.ConclusionsThis observational study suggests that treatment with GLP-1RA and SGLT-2i result in very similar cardiorenal outcomes. In the short term, treatment with GLP-1RA seem to be associated with lower risks of stroke and peripheral artery disease, whereas SGLT-2i seem to be nominally associated with lower risk of heart failure and total mortality.

Dataset Information

Evolving channeling in prescribing SGLT-2 inhibitors as first-line treatment for type 2 diabetes.

Purpose

Methods

Results

Conclusions

Publications

Evolving channeling in prescribing SGLT-2 inhibitors as first-line treatment for type 2 diabetes.

Similar Datasets

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