Latest Evidence on Sulfonylureas: What’s New?

Leiter, Lawrence A.

doi:10.1007/s13300-020-00812-2

Cited by 10 publications

(4 citation statements)

References 23 publications

(29 reference statements)

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“…Sulfonylureas are generally not recommended in patients with obesity, due to significant risk of hypoglycaemia, weight gain, reduced efficacy, and the need for careful dose titration in patients with renal disease[ 67 ]. Hypoglycaemia risk has been reported to vary between sulfonylurea agents, with gliclazide having the lowest reported incidence among this class of medications[ 68 ]. Usually prescribed in combination with other agents, sulfonylureas have been reported to result in weight gain of approximately 2.01-2.3 kg[ 63 , 69 ].…”

Section: Drug Therapymentioning

confidence: 99%

Management of diabesity: Current concepts

Michaelidou¹,

Pappachan²,

Jeeyavudeen³

2023

World J Diabetes

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The global prevalence of obesity is increasing rapidly with an exponential rise in incidence of type 2 diabetes mellitus in recent years. ‘Diabesity’, the term coined to show the strong interlink between obesity and diabetes, is the direct cons-equence of the obesity pandemic, and poses significant challenges in the management of the disease. Without addressing the clinical and mechanistic complications of obesity such as metabolic-associated fatty liver disease and obstructive sleep apnoea, a rational management algorithm for diabesity cannot be developed. Several classes of anti-diabetic medications including insulins, sulphonylureas, thiazolidinediones and meglitinides are associated with the risk of weight gain and may potentially worsen diabesity. Therefore, appropriate selection of antidiabetic drug regimen is crucial in the medical management of diabesity. The role of non-pharmacological measures such as dietary adjustments, exercise interventions and bariatric procedures should also be emphasised. Unfortunately, the importance of appropriate and optimal management of diabesity is often overlooked by medical professionals when achieving adequate glycemic control which results in inappropriate management of the disease and its complications. This review provides a narrative clinical update on the evidence behind the management of diabesity.

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Section: Drug Therapymentioning

confidence: 99%

Management of diabesity: Current concepts

Michaelidou¹,

Pappachan²,

Jeeyavudeen³

2023

World J Diabetes

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“…The new‐generation SUs (such as gliclazide) displayed lower hypoglycaemia and weight gain rates, with improved cardiovascular and renal safety. SUs remain a popular choice of treatment in countries without a well‐established healthcare system and where costs are a major issue 102 …”

Section: Considerations For Treatment Of Newly Diagnosed T2d In the Ementioning

confidence: 99%

“…SUs remain a popular choice of treatment in countries without a well-established healthcare system and where costs are a major issue. 102 Table 4 shows findings from clinical trials with initial combination therapy conducted in Asian populations. The combination of a DPP4-i and metformin was the most commonly investigated treatment with confirmed efficacy in reducing HbA1c.…”

Section: Treatment For Newly Diagnosed T2d In East Asiamentioning

confidence: 99%

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: AnEast Asianperspective

Chan

et al. 2020

Diabetes Obesity Metabolism

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Type 2 diabetes (T2D) in the East Asian population is characterized by phenotypes such as low body mass index, an index of β‐cell dysfunction, and higher percentage of body fat, an index of insulin resistance. These phenotypes/pathologies may predispose people to early onset of diabetes with increased risk of stroke and renal disease. Less than 50% of patients with T2D in East Asia achieve glycaemic targets recommended by national or regional guidelines, which may be attributable to knowledge and/or implementation gaps. Herein, we review the latest evidence with special reference to East Asian patients with T2D and present arguments for the need to use early combination therapy to intensify glycaemic control. This strategy is supported by the 5‐year worldwide VERIFY study, which reported better glycaemic durability in newly diagnosed patients with T2D with a mean HbA1c of 6.9% treated with early combination therapy of vildagliptin plus metformin versus those treated with initial metformin monotherapy followed by addition of vildagliptin only with worsening glycaemic control. This paradigm shift of early intensified treatment is now recommended by the American Diabetes Association and the European Association for the Study of Diabetes. In order to translate these evidence to practice, increased awareness and strengthening of the healthcare system are needed to diagnose and manage patients with T2D early for combination therapy.

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“…[7][8][9][10][11][12][13][14] While older antihyperglycemic agents, like sulfonylureas (SUs), have not undergone similarly comprehensive trials to evaluate their cardiovascular efficacy or safety, some studies suggested their neutral effect on cardiovascular outcomes and risk of hypoglycemia. [15][16][17] Furthermore, direct comparisons of SGLT2is and GLP1-RAs with dipeptidyl peptidase-4 inhibitors (DPP4is), which are antihyperglycemic agents with neutral effects on MACE, have not been conducted and no major trials are in progress. Nevertheless, DPP4is and SUs continue to be used in clinical practice and are recommended as second-line T2DM agents in national clinical practice guidelines.…”

Section: Introductionmentioning

confidence: 99%

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

Khera,

Aminorroaya,

Dhingra

et al. 2024

Preprint

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BackgroundSGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP1-RAs) reduce major adverse cardiovascular events (MACE) in patients with type 2 diabetes mellitus (T2DM). However, their effectiveness relative to each other and other second-line antihyperglycemic agents is unknown, without any major ongoing head-to-head trials.MethodsAcross the LEGEND-T2DM network, we included ten federated international data sources, spanning 1992-2021. We identified 1,492,855 patients with T2DM and established cardiovascular disease (CVD) on metformin monotherapy who initiated one of four second-line agents (SGLT2is, GLP1-RAs, dipeptidyl peptidase 4 inhibitor [DPP4is], sulfonylureas [SUs]). We used large-scale propensity score models to conduct an active comparator, target trial emulation for pairwise comparisons. After evaluating empirical equipoise and population generalizability, we fit on-treatment Cox proportional hazard models for 3-point MACE (myocardial infarction, stroke, death) and 4-point MACE (3-point MACE + heart failure hospitalization) risk, and combined hazard ratio (HR) estimates in a random-effects meta-analysis.FindingsAcross cohorts, 16·4%, 8·3%, 27·7%, and 47·6% of individuals with T2DM initiated SGLT2is, GLP1-RAs, DPP4is, and SUs, respectively. Over 5·2 million patient-years of follow-up and 489 million patient-days of time at-risk, there were 25,982 3-point MACE and 41,447 4-point MACE events. SGLT2is and GLP1-RAs were associated with a lower risk for 3-point MACE compared with DPP4is (HR 0·89 [95% CI, 0·79-1·00] and 0·83 [0·70-0·98]), and SUs (HR 0·76 [0·65-0·89] and 0·71 [0·59-0·86]). DPP4is were associated with a lower 3-point MACE risk versus SUs (HR 0·87 [0·79-0·95]). The pattern was consistent for 4-point MACE for the comparisons above. There were no significant differences between SGLT2is and GLP1-RAs for 3-point or 4-point MACE (HR 1·06 [0·96-1·17] and 1·05 [0·97-1·13]).InterpretationIn patients with T2DM and established CVD, we found comparable cardiovascular risk reduction with SGLT2is and GLP1-RAs, with both agents more effective than DPP4is, which in turn were more effective than SUs. These findings suggest that the use of GLP1-RAs and SGLT2is should be prioritized as second-line agents in those with established CVD.FundingNational Institutes of Health, United States Department of Veterans Affairs

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Latest Evidence on Sulfonylureas: What’s New?

Cited by 10 publications

References 23 publications

Management of diabesity: Current concepts

Management of diabesity: Current concepts

Early combination versus initial metformin monotherapy in the management of newly diagnosed type 2 diabetes: AnEast Asianperspective

Comparative Effectiveness of Second-line Antihyperglycemic Agents for Cardiovascular Outcomes: A Large-scale, Multinational, Federated Analysis of the LEGEND-T2DM Study

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