Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the <scp>ADJUNCT ONE</scp> and <scp>ADJUNCT TWO</scp> randomized controlled trials

Dejgaard, Thomas F.; Scholten, Bernt Johan von; Christiansen, Erik; Kreiner, Frederik Flindt; Bardtrum, Lars; Herrath, Matthias von; Mathieu, Chantal; Madsbad, Sten; one,; Investigators, Two

doi:10.1111/dom.14532

Cited by 27 publications

(20 citation statements)

References 36 publications

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“…A post hoc analysis of the studies revealed that the efficacy of liraglutide in reducing HbA 1c did not depend on baseline body weight and glycemic control subgroups. However, residual β-cell function was associated with a significant impact on HbA 1c reduction and the risk of hypoglycemia [69]. Adverse events were higher in the liraglutide groups and were mainly related to the gastrointestinal system.…”

Section: Glp1-receptor Agonistsmentioning

confidence: 93%

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

et al. 2022

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Background: In Type 1 diabetes (T1D), according to the most recent guidelines, the everyday glucose-lowering treatment is still restricted to the use of subcutaneous insulin, while multiple therapeutic options exist for Type 2 diabetes (T2D). Methods: For this narrative review we unsystematically screened PubMed and Embase to identify clinical trials which investigated glucose-lowering agents as an adjunct to insulin treatment in people with T1D. Published studies up to March 2022 were included. We discuss the safety and efficacy in modifying cardiovascular risk factors for each drug, the current status of research, and provide a clinical perspective. Results: For several adjunct agents, in T1D, the scientific evidence demonstrates improvements in HbA1c, reductions in the risk of hypoglycemia, and achievements of lower insulin requirements, as well as positive effects on cardiovascular risk factors, such as blood lipids, blood pressure, and weight. As the prevalence of obesity, the major driver for double diabetes, is rising, weight and cardiovascular risk factor management is becoming increasingly important in people with T1D. Conclusions: Adjunct glucose-lowering agents, intended to be used in T2D, bear the potential to beneficially impact on cardiovascular risk factors when investigated in the T1D population and are suggested to be more extensively considered as potentially disease-modifying drugs in the future and should be investigated for hard cardiovascular endpoints.

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Section: Glp1-receptor Agonistsmentioning

confidence: 93%

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

et al. 2022

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“…For anti-IL-21 antibody targeting IL-21, early clinical trials did not reflect significant safety risks or significant changes in laboratory safety parameters [98]. Glucagon-like peptide-1 receptor (GLP-1R) agonists liraglutide has been suggested to preserve functional beta cells by reducing metabolic stresses and preventing apoptosis [99]. Therefore, combined treatment could enable beta-cell survival with a reduced risk of complications compared with traditional immunomodulation.…”

Section: Combination Immunomodulatory and Beta-cell Therapymentioning

confidence: 99%

Recent Advances in Immune-Based Therapies for Type 1 Diabetes

Schweiger¹

2022

Horm Res Paediatr

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Background: Type 1 diabetes (T1D) is a chronic autoimmune disease characterized by progressive destruction of the pancreatic beta-cells leading to a lifelong dependence on insulin. It is associated with an increased morbidity and mortality from diabetes-related complications and a significant treatment burden. However, there has been a substantial progress in therapeutic strategies that can affect the course of the disease. Summary: This review addresses advances in immunotherapy aimed at preserving residual beta-cell function in individuals with a recent onset of T1D, and arresting the disease in pre-symptomatic stages. Recent and ongoing clinical trials have investigated the efficacy and safety of various immunotherapeutic strategies aimed at targeting several mechanisms of autoimmunity, which are thought to be important in disease pathogenesis, and therapies that also address beta cell health. So far, T cell-directed therapies that led to a favourable balance between T effector cell depletion or modulation and preservation or expansion of regulatory T cells have shown the most success. Furthermore, regarding the timing of intervention, teplizumab was the first immunomodulatory agent to demonstrate a significant delay in disease progression in high-risk individuals before clinical onset. Key Messages: As more targeted immune interventions with potentially fewer side effects are closer to the translation into clinical practice, some new challenges may need to be addressed. The use of combination approaches that include immunotherapeutic strategies targeting different aspects of the immune system and interventions that improve beta cell health may be required, along with the use of individualized patient-tailored approaches, a move towards early intervention, and a focus on patient-reported outcome measures.

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“…These beneficial effects observed in type 2 diabetes have encouraged some physicians to initiate GLP1-RA and/or SGLT2i in people with type 1 diabetes. Previous studies evaluated the efficacies and safety of GLP1-RA and SGLT2i therapy in individuals with type 1 diabetes, but the combination of the medications is not yet described [14][15][16][17]. In clinical trials, the addition of GLP1-RA liraglutide to insulin led to a reduction in glycated hemoglobin (HbA1c), body weight, and total insulin dose; however, episodes of hypoglycemia or hyperglycemia with ketosis increased [14,15].…”

Section: Introductionmentioning

confidence: 99%

“…Previous studies evaluated the efficacies and safety of GLP1-RA and SGLT2i therapy in individuals with type 1 diabetes, but the combination of the medications is not yet described [14][15][16][17]. In clinical trials, the addition of GLP1-RA liraglutide to insulin led to a reduction in glycated hemoglobin (HbA1c), body weight, and total insulin dose; however, episodes of hypoglycemia or hyperglycemia with ketosis increased [14,15]. Similarly, adding SGLT2i dapagliflozin to insulin therapy was associated with improved HbA1c and reduced body weight and insulin dose [16][17][18].…”

Section: Introductionmentioning

confidence: 99%

Glucagon‐like peptide‐1 agonists combined with sodium‐glucose cotransporter‐2 inhibitors reduce weight in type 1 diabetes

Al-Ozairi

Irshad

Taghadom

et al. 2023

Obesity

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ObjectiveThis study evaluated whether adding sodium‐glucose cotransporter‐2 inhibitors (SGLT2i) and/or glucagon‐like peptide‐1 receptor agonists (GLP1‐RA) to insulin reduced weight and glycemia in people with type 1 diabetes.MethodsThis retrospective analysis of electronic health records evaluated 296 people with type 1 diabetes over 12 months after medications were first prescribed. Four groups were defined: control n = 80, SGLT2i n = 94, GLP1‐RA n = 82, and combination of drugs (Combo) n = 40. We measured changes at 1 year in weight and glycated hemoglobin (HbA1c).ResultsThe control group did not have changes in weight or glycemic control. The mean (SD) percentage weight loss after 12 months was 4.4% (6.0%), 8.2% (8.5%), and 9.0% (8.4%) in the SGLT2i, GLP1‐RA, and Combo groups, respectively (p < 0.001). The Combo group lost the most weight (p < 0.001). The HbA1c reduction was 0.4% (0.7%), 0.3% (0.7%), and 0.6% (0.8%) in the SGLT2i, GLP1‐RA, and Combo groups, respectively (p < 0.001). The Combo group had the biggest improvements in glycemic control and total and low‐density lipoprotein cholesterol compared with baseline (all p < 0.01). Severe adverse events were similar between all the groups, with no increased risk of diabetic ketoacidosis.ConclusionsThe SGLT2i and GLP1‐RA agents on their own improved body weight and glycemia, but combining the medications resulted in more weight loss. Treatment intensification appears to result in benefits with no difference in severe adverse events.

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Efficacy and safety of liraglutide in type 1 diabetes by baseline characteristics in the ADJUNCT ONE and ADJUNCT TWO randomized controlled trials

Cited by 27 publications

References 36 publications

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

Glucose-Lowering Therapy beyond Insulin in Type 1 Diabetes: A Narrative Review on Existing Evidence from Randomized Controlled Trials and Clinical Perspective

Recent Advances in Immune-Based Therapies for Type 1 Diabetes

Glucagon‐like peptide‐1 agonists combined with sodium‐glucose cotransporter‐2 inhibitors reduce weight in type 1 diabetes

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