Glucagon in type 1 diabetes patients receiving SGLT2 inhibitors: A Friend or Foe?

Fukui, Tetsuya; Ohara, Makoto; Yamagishi, Sho‐ichi

doi:10.1002/dmrr.3415

Cited by 4 publications

(5 citation statements)

References 28 publications

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“…Other investigations have shown that SGLT2 inhibitors significantly increased fasting glucagon levels in T1D. 31,32 In the present study, the participants did not take ipragliflozin in the morning of each MMTT, and they were allowed to use bolus insulin up to 4 h before each MMTT in order to maintain their fasting plasma glucose level at <11.1 mmol/L. These aspects might have resulted in an underestimate of the elevations of fasting glucagon levels compared with real-world clinical practice.…”

Section: Discussionmentioning

confidence: 87%

“…Unlike the postprandial glucagon responses, the fasting glucagon levels were not significantly increased by the ipragliflozin treatment in this study. Other investigations have shown that SGLT2 inhibitors significantly increased fasting glucagon levels in T1D 31,32 . In the present study, the participants did not take ipragliflozin in the morning of each MMTT, and they were allowed to use bolus insulin up to 4 h before each MMTT in order to maintain their fasting plasma glucose level at <11.1 mmol/L.…”

Section: Discussionmentioning

confidence: 91%

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Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study

Nakamura,

Horie,

Kitamura

et al. 2024

Diabetes Obesity Metabolism

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AimClinical trials showed the efficacy of sodium‐glucose cotransporter 2 inhibitors for type 1 diabetes (T1D) by significant reductions in body weight and glycaemic variability, but elevated susceptibility to ketoacidosis via elevated glucagon secretion was a potential concern. The Suglat‐AID evaluated glucagon responses and its associations with glycaemic control and ketogenesis before and after T1D treatment with the sodium‐glucose cotransporter 2 inhibitor, ipragliflozin.MethodsAdults with T1D (n = 25) took 50‐mg open‐labelled ipragliflozin daily as adjunctive to insulin. Laboratory/clinical data including continuous glucose monitoring were collected until 12 weeks after the ipragliflozin initiation. The participants underwent a mixed‐meal tolerance test (MMTT) twice [before (first MMTT) and 12 weeks after ipragliflozin treatment (second MMTT)] to evaluate responses of glucose, C‐peptide, glucagon and β‐hydroxybutyrate.ResultsThe area under the curve from fasting (0 min) to 120 min (AUC0‐120min) of glucagon in second MMTT were significantly increased by 14% versus first MMTT. The fasting and postprandial β‐hydroxybutyrate levels were significantly elevated in second MMTT versus first MMTT. The positive correlation between postprandial glucagon secretion and glucose excursions observed in first MMTT disappeared in second MMTT, but a negative correlation between fasting glucagon and time below range (glucose, <3.9 mmol/L) appeared in second MMTT. The percentage changes in glucagon levels (fasting and AUC0‐120min) from baseline to 12 weeks were significantly correlated with those in β‐hydroxybutyrate levels.ConclusionsIpragliflozin treatment for T1D increased postprandial glucagon secretion, which did not exacerbate postprandial hyperglycaemia but might protect against hypoglycaemia, leading to reduced glycaemic variability. The increased glucagon secretion might accelerate ketogenesis when adequate insulin is not supplied.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 91%

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study

Nakamura,

Horie,

Kitamura

et al. 2024

Diabetes Obesity Metabolism

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“…Furthermore, potential differences in average efficacy on HbA1c between SGLT2 inhibitors and GLP1 receptor agonists could have affected results, since the same definition of success was adopted for the two classes. Additionally, some parameters potentially affecting drug response (e.g., glucagon secretion for patients receiving SGLT2 inhibitors 28 ) were not assessed. Finally, differences between reported and actually administered drugs could not be detected by the present study, in which current treatment was based on patients' interviews during follow‐up visits; therefore, this study cannot incorporate data on compliance and/or adherence to the prescribed treatment.…”

Section: Discussionmentioning

confidence: 99%

Predictors of efficacy of Sodium‐GLucose Transporter‐2 inhibitors and Glucagon‐Like Peptide 1 receptor agonists: A retrospective cohort study

Scoccimarro,

Cipani,

Dicembrini

et al. 2023

Diabetes Metabolism Res

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AimsThe aim of the present study was to verify predictors of HbA1c reduction with Sodium‐GLucose Transporter‐2 (SGLT2) inhibitors and Glucagon‐Like Peptide 1 (GLP1) receptor agonists in routine clinical practice.Materials and MethodsA retrospective cohort study was performed, enrolling patients with type 2 diabetes aged ≥18 years who received a prescription of an SGLT2 inhibitor or a long‐acting GLP1 receptor agonist with at least 6 months of persistence in therapy. Therapeutic success was defined as HbA1c reduction >10 mmol/mol or attainment of the recommended HbA1c target.ResultsOut of 236 patients receiving SGLT2 inhibitors, 148 were categorised as successes: successes had a mean lower age and higher estimated Glomerular Filtration Rate than failures, but only age retained statistical significance at multivariate analysis (Odds Ratio with 95% confidence interval: 0.94 [0.91–0.98], p = 0.006). In the GLP1 receptor agonists cohort (N = 214) there were 146 successes, showing a significantly shorter duration of diabetes even after adjusting for age, and baseline HbA1c (HR 0.96 [0.91–0.99], p = 0.02).ConclusionsThe present study is a preliminary exploration of factors associated with HbA1c response to SGLT2 inhibitors and GLP1 receptor agonists. Differences in predictors of HbA1c changes across different classes of drugs could be useful in identifying the most suitable drug in individual patients. SGLT2 inhibitors seem to be associated with a greater reduction of HbA1c in younger subjects, and GLP1 agonists in those with a shorter duration of diabetes.

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“…In these large, placebo-controlled studies, a novel class of antidiabetic agents, the sodium-glucose cotransporter-2 (SGLT-2) inhibitors, have been shown to improve cardiovascular and renal outcomes, including a decrease in the incidence of heart failure, cardiovascular death, and reduced risk of renal events [10,41,77]. Inhibitors of SGLT-2 are oral glucose-lowering medications that enhance the excretion of glucose through the urine by inhibiting glucose reuptake at the proximal renal tubules, thereby lowering blood glucose levels in an insulin-independent way, while simultaneously decreasing blood pressure and body weight in patients with T2DM [21,63,69]. Following the initiation of the therapy with SGLT-2 inhibitors, there is a rapid onset of the renal and cardiovascular benefits, therefore it is considered that mechanisms other than optimizing blood glucose levels are involved in the development of these effects, since improvement in glycaemic control would probably take years to have a detectable impact [10].…”

Section: Introductionmentioning

confidence: 99%

“…Additionally, SGLT2 inhibitors are not recommended in type 1 diabetes mellitus treatment. Furthermore, there are some circumstances, such as volume depletion, hypotension, active genital infections and diabetic ketoacidosis where the use of SGLT2 inhibitors should be temporarily interrupted until these conditions are solved[3,21,87]. Regarding drug interactions, these are a key concern in diabetes care as most individuals with T2D receive multiple medications simultaneously.…”

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confidence: 99%

New Directions in Pharmacological Treatment With SGLT-2 Inhibitor Molecules in the Light of Current Guidelines for Diabetes Mellitus, Heart Failure and Kidney Disease

TILINCA

2023

FARMACIA

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Sodium-glucose cotransporter-2 (SGLT-2) inhibitors, a newer class of oral anti-hyperglycaemic agents, have been shown to improve cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), by reducing the risk of heart failure, cardiovascular death, and renal events. This review aimed to describe the mechanism of action and clinical benefits of SGLT-2 inhibitors, highlighting their cardiorenal protection, glucose lowering effects, and their efficacy in the management of T2DM with multiple risk factors. SGLT-2 inhibitors reduce the reabsorption of sodium and glucose from the proximal tubules, thereby increasing renal glucose and sodium excretion. In addition to their glucose-lowering property, the clinical benefits of SGLT-2 inhibitors involve weight loss and major cardio-and reno-protective effects such as decreased preload and afterload, reversed cardiac remodelling, improved endothelial function, reduced albuminuria, improved glomerular hemodynamic and preserved kidney function. Therefore, SGLT2 inhibitors are a crucial component of management guidelines for diabetes, heart failure and chronic kidney disease, even in those without T2DM. RezumatInhibitorii co-transportorului 2 de sodiu-glucoză (SGLT-2), o nouă clasă de agenți antihiperglicemianți cu administrare orală, au demonstrat îmbunătățirea rezultatelor cardiovasculare și renale la pacienți cu diabet zaharat (DZ) tip 2, prin reducerea riscului de insuficiență cardiacă, deces de origine cardiovasculară și complicații renale. Acest articol își propune descrierea mecanismului de acțiune și a beneficiilor clinice ale inhibitorilor de SGLT-2, evidențiind efectele lor protectoare cardiorenale și de scădere a glicemiei, precum și eficacitatea lor în managementul DZ tip 2 cu multipli factori de risc. Inhibitorii de SGLT-2 reduc reabsorbția sodiului și glucozei din tubii contorți proximali, crescând astfel excreția renală de glucoză și sodiu. Pe lângă scăderea glicemiei, beneficiile clinice ale inhibitorilor de SGLT-2 includ scăderea în greutate și efecte cardio-și renoprotectoare, precum scăderea presarcinii și postsarcinii cardiace, inversarea remodelării cardiace majore, îmbunătățirea funcției endoteliale, reducerea albuminuriei, ameliorarea hemodinamicii glomerulare și menținerea funcției renale. Astfel, inhibitorii de SGLT-2 reprezintă un pilon extrem de important al ghidurilor de management, atât pentru diabetul zaharat, cât și pentru insuficiența cardiacă și boala renală cronică, chiar și la cei fără DZ tip 2.

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Glucagon in type 1 diabetes patients receiving SGLT2 inhibitors: A Friend or Foe?

Cited by 4 publications

References 28 publications

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study

Glucagon secretion and its association with glycaemic control and ketogenesis during sodium‐glucose cotransporter 2 inhibition by ipragliflozin in people with type 1 diabetes: Results from the multicentre, open‐label, prospective study

Predictors of efficacy of Sodium‐GLucose Transporter‐2 inhibitors and Glucagon‐Like Peptide 1 receptor agonists: A retrospective cohort study

New Directions in Pharmacological Treatment With SGLT-2 Inhibitor Molecules in the Light of Current Guidelines for Diabetes Mellitus, Heart Failure and Kidney Disease

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