First-Line Therapy for Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

Choi, Jin; Winn, Aaron N.; Skandari, M. Reza; Franco, Melissa; Staab, Erin M.; Alexander, Jason; Wan, Wen; Zhu, Mengqi; Huang, Elbert S.; Philipson, Louis H.; Laiteerapong, Neda

doi:10.7326/m21-2941

Cited by 47 publications

(26 citation statements)

References 56 publications

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“…From a clinical perspective, reliable and easy-to-use CPMs could help diabetologists and cardiologists to prioritise a more targeted evaluation (eg, echocardiography, biomarker screening) and HF preventive interventions (eg, lifestyle interventions, blood pressure control, sodium-glucose co-transporter 2 inhibitors) in those at higher risk, in a cost-effective manner, while avoiding drugs that may increase the individual risk for HF (eg, pioglitazone, saxagliptin) 1 46 47. Identification of low-risk individuals, on the contrary, could avoid unnecessary and costly interventions.…”

Section: Discussionmentioning

confidence: 99%

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis

Kostopoulos

Doundoulakis

Toulis

et al. 2023

Heart

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ObjectiveTo provide a systematic review, critical appraisal, assessment of performance and generalisability of all the reported prognostic models for heart failure (HF) in patients with type 2 diabetes (T2D).MethodsWe performed a literature search in Medline, Embase, Central Register of Controlled Trials, Cochrane Database of Systematic Reviews and Scopus (from inception to July 2022) and grey literature to identify any study developing and/or validating models predicting HF applicable to patients with T2D. We extracted data on study characteristics, modelling methods and measures of performance, and we performed a random-effects meta-analysis to pool discrimination in models with multiple validation studies. We also performed a descriptive synthesis of calibration and we assessed the risk of bias and certainty of evidence (high, moderate, low).ResultsFifty-five studies reporting on 58 models were identified: (1) models developed in patients with T2D for HF prediction (n=43), (2) models predicting HF developed in non-diabetic cohorts and externally validated in patients with T2D (n=3), and (3) models originally predicting a different outcome and externally validated for HF (n=12). RECODe (C-statistic=0.75 95% CI (0.72, 0.78), 95% prediction interval (PI) (0.68, 0.81); high certainty), TRS-HFDM (C-statistic=0.75 95% CI (0.69, 0.81), 95% PI (0.58, 0.87); low certainty) and WATCH-DM (C-statistic=0.70 95% CI (0.67, 0.73), 95% PI (0.63, 0.76); moderate certainty) showed the best performance. QDiabetes-HF demonstrated also good discrimination but was externally validated only once and not meta-analysed.ConclusionsAmong the prognostic models identified, four models showed promising performance and, thus, could be implemented in current clinical practice.

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Section: Discussionmentioning

confidence: 99%

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis

Kostopoulos

Doundoulakis

Toulis

et al. 2023

Heart

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“…receptor agonist can potentially be an effective second-line therapy to treat type 2 diabetes. 5,38 The US Food and Drug Administration approved tirzepatide injection to improve blood sugar control in adults with type 2 diabetes in May 2020. However, the economic value of tirzepatide needs to be assessed before including it in the formulary.…”

Section: Discussionmentioning

confidence: 99%

5‐Year simulation of diabetes‐related complications in people treated with tirzepatide or semaglutide versus insulin glargine

Niu,

Alkhuzam,

Guan

et al. 2023

Diabetes Obesity Metabolism

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AimThis study compared the 5‐year incidence rate of macrovascular and microvascular complications for tirzepatide, semaglutide and insulin glargine in individuals with type 2 diabetes, using the Building, Relating, Assessing, and Validating Outcomes (BRAVO) diabetes simulation model.Research Design and MethodsThis study was a 5‐year SURPASS‐2 trial extrapolation, with an insulin glargine arm added as an additional comparator. The 1‐year treatment effects of tirzepatide (5, 10 or 15 mg), semaglutide (1 mg) and insulin glargine on glycated haemoglobin, systolic blood pressure, low‐density lipoprotein and body weights were obtained from the SUSTAIN‐4 and SURPASS‐2 trials. We used the BRAVO model to predict 5‐year complications for each study arm under two scenarios: the 1‐year treatment effects persisted (optimistic) or diminished to none in 5 years (conservative).ResultsWhen compared with insulin glargine, we projected a 5‐year risk reduction in cardiovascular adverse events [rate ratio (RR) 0.64, 95% confidence interval (CI) 0.61‐0.67] and microvascular composite (RR 0.67, 95% CI 0.64‐0.70) with 15 mg tirzepatide, and 5‐year risk reduction in cardiovascular adverse events (RR 0.75, 95% CI 0.72‐0.79) and microvascular composite (RR 0.79, 95% CI 0.76‐0.82) with semaglutide (1 mg) under an optimistic scenario. Lower doses of tirzepatide also had similar, albeit smaller benefits. Treatment effects for tirzepatide and semaglutide were smaller but still significantly higher than insulin glargine under a conservative scenario. The 5‐year risk reduction in diabetes‐related complication events and mortality for the 15 mg tirzepatide compared with insulin glargine ranged from 49% to 10% under an optimistic scenario, which was reduced by 17%‐33% when a conservative scenario was assumed.ConclusionWith the use of the BRAVO diabetes model, tirzepatide and semaglutide exhibited potential to reduce the risk of macrovascular and microvascular complications among individuals with type 2 diabetes, compared with insulin glargine in a 5‐year window. Based on the current modelling assumptions, tirzepatide (15 mg) may potentially outperform semaglutide (1 mg). While the BRAVO model offered insights, the long‐term cardiovascular benefit of tirzepatide should be further validated in a prospective clinical trial.

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“…As first-line agents, SGLT-2 inhibitors and GLP-1 receptor agonists would improve type 2 diabetes outcomes, but they are probably not cost-effective compared to metformin due to their high medication costs [54]. However, several studies showed that SGLT-2 inhibitors and GLP-1 receptor agonists as an add-on therapy to metformin are cost-effective and maybe cost-saving compared to other antidiabetic drugs [55].…”

Section: Cost Of Antidiabetic Medications and Cost-effectiveness-anal...mentioning

confidence: 99%

Swiss recommendations of the Society for Endocrinology and Diabetes (SGED/SSED) for the treatment of type 2 diabetes mellitus (2023)

Gastaldi¹,

Leggett²,

Thalmann³

et al. 2023

Swiss Med Wkly

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As a first step, the authors emphasise lifestyle changes (increased physical activity, stopping smoking), blood pressure control, and lowering cholesterol). The initial medical treatment should always be a combination treatment with metformin and a sodium-glucose transporter 2 (SGLT-2) inhibitor or a glucagon-like 1 peptide (GLP-1) receptor agonist. Metformin is given first and up-titrated, followed by SGLT-2 inhibitors or GLP-1 receptor agonists. In persons with type 2 diabetes, if the initial double combination is not sufficient, a triple combination (SGLT-2 inhibitor, GLP-1 receptor agonist, and metformin) is recommended. This triple combination has not been officially tested in cardiovascular outcome trials, but there is more and more real-world experience in Europe and in the USA that proves that the triple combination with metformin, SGLT-2 inhibitor, and GLP-1 receptor agonist is the best treatment to reduce 3-point MACE, total mortality, and heart failure as compared to other combinations. The treatment with sulfonylurea is no longer recommended because of its side effects and higher mortality compared to the modern treatment with SGLT-2 inhibitors and GLP-1 receptor agonists. If the triple combination is not sufficient to reduce the HbA1c to the desired target, insulin treatment is necessary. A quarter of all patients with type 2 diabetes (sometimes misdiagnosed) require insulin treatment. If insulin deficiency is the predominant factor at the outset of type 2 diabetes, the order of medications has to be reversed: insulin first and then cardio-renal protective medications (SGLT-2 inhibitors, GLP-1 receptor agonists).

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First-Line Therapy for Type 2 Diabetes With Sodium–Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists

Cited by 47 publications

References 56 publications

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis

Prognostic models for heart failure in patients with type 2 diabetes: a systematic review and meta-analysis

5‐Year simulation of diabetes‐related complications in people treated with tirzepatide or semaglutide versus insulin glargine

Swiss recommendations of the Society for Endocrinology and Diabetes (SGED/SSED) for the treatment of type 2 diabetes mellitus (2023)

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