<scp>Real‐world</scp> data of 12‐month adjunct sodium‐glucose co‐transporter‐2 inhibitor treatment in type 1 diabetes from the <scp>German/Austrian DPV</scp> registry: Improved <scp>HbA1c</scp> without diabetic ketoacidosis

Seufert, Jochen; Lanzinger, Stefanie; Danne, Thomas; Bramlage, Peter; Schmid, Sebastian; Kopp, Florian; Kreß, Stephan; Fasching, Peter; Schäfer, Claus; Holl, Reinhard W.

doi:10.1111/dom.14620

Cited by 17 publications

(23 citation statements)

References 9 publications

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“…SGLT2 inhibitors were first introduced in clinical practice to reduce renal glucose reabsorption and decrease plasma glucose levels. Therefore, clinicians were concerned that loss of urinary glucose could reduce body weight and impair physical status in lean patients with Type 1 DM [14,50]. In fact, only recently has the European Medicines Agency approved SGLT2 inhibition in Type 1 diabetes in addition to the current therapy in individuals with a body mass index ≥ 27 kg/m 2 [51].…”

Section: Discussionmentioning

confidence: 99%

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

et al. 2022

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Clinical trials have shown that sodium glucose co-transporter 2 (SGLT2) inhibitors improve clinical outcomes in diabetes mellitus (DM) patients. As most studies were performed in Type 2 DM, the cardiovascular effects of SGLT2 inhibition still require clarification in Type 1 DM. We analyzed the effects of SGLT2 inhibitor dapagliflozin on cardiac remodeling in rats with streptozotocin-induced diabetes, an experimental model of Type 1 DM. Methods: Male Wistar rats were assigned into four groups: control (C, n = 14); control treated with dapagliflozin (C + DAPA, n = 14); diabetes (DM, n = 20); and diabetes treated with dapagliflozin (DM + DAPA, n = 20) for 8 weeks. Dapagliflozin dosage was 5 mg/kg/day. Statistical analyses: ANOVA and Tukey or Kruskal–Wallis and Dunn. Results: DM + DAPA presented decreased blood pressure and glycemia and increased body weight compared to DM (C 507 ± 52; C + DAPA 474 ± 50; DM 381 ± 52 *; DM + DAPA 430 ± 48 # g; * p < 0.05 vs. C; # p < 0.05 vs. C + DAPA and DM + DAPA). DM echocardiogram presented left ventricular and left atrium dilation with impaired systolic and diastolic function. Cardiac changes were attenuated by dapagliflozin. Myocardial hydroxyproline concentration and interstitial collagen fraction did not differ between groups. The expression of Type III collagen was lower in DM and DM + DAPA than their controls. Type I collagen expression and Type I-to-III collagen ratio were lower in DM + DAPA than C + DAPA. DM + DAPA had lower lipid hydroperoxide concentration (C 275 ± 42; C + DAPA 299 ± 50; DM 385 ± 54 *; DM + DAPA 304 ± 40 # nmol/g tissue; * p < 0.05 vs. C; # p < 0.05 vs. DM) and higher superoxide dismutase and glutathione peroxidase activity than DM. Advanced glycation end products did not differ between groups. Conclusion: Dapagliflozin is safe, increases body weight, decreases glycemia and oxidative stress, and attenuates cardiac remodeling in an experimental rat model of Type 1 diabetes mellitus.

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Section: Discussionmentioning

confidence: 99%

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

et al. 2022

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“…Recognising these benefits, the European Medicines Agency (EMA) approved dapagliflozin 5 mg in March 2019 as an adjunct in the treatment of individuals with type 1 diabetes with overweight 14 . Subsequent real‐world studies from Europe found improved glycaemia without the expected increase in insulin dose that is required to achieve normoglycaemia, and without the weight gain that is usually observed with treatment intensification 15 . While the EMA’s decision was celebrated by diabetologists across the globe, support was not replicated by the FDA, which declined applications for dapagliflozin and empagliflozin largely due to risk concerns 16…”

Section: Sglt2 Inhibitors In Type 1 Diabetes: Therapeutic and Regulat...mentioning

confidence: 99%

“…EMA approval of dapagliflozin was conditional on mandatory provision of a strict risk mitigation strategy by prescribers. Reassuringly, early real‐world evidence from European registry data showed no increase in DKA risk 15 . In light of the initial enthusiasm and safety of low dose SGLT2 inhibitors in type 1 diabetes, we and others were concerned to learn that EMA approval was abruptly reversed in October 2021 19,20 .…”

Section: Sglt2 Inhibitors In Type 1 Diabetes: Therapeutic and Regulat...mentioning

confidence: 99%

“…14 Subsequent real-world studies from Europe found improved glycaemia without the expected increase in insulin dose that is required to achieve normoglycaemia, and without the weight gain that is usually observed with treatment intensification. 15 While the EMA's decision was celebrated by diabetologists across the globe, support was not replicated by the FDA, which declined applications for dapagliflozin and empagliflozin largely due to risk concerns. 16 Diabetic ketoacidosis (DKA), a serious diabetic emergency necessitating hospital management, is the main factor hindering regulatory approval of SGLT2 inhibitors in type 1 diabetes.…”

Section: Sglt2 Inhibitors In Type 1 Diabetes: Therapeutic and Regulat...mentioning

confidence: 99%

“…Reassuringly, early real-world evidence from European registry data showed no increase in DKA risk. 15 In light of the initial enthusiasm and safety of low dose SGLT2 inhibitors in type 1 diabetes, we and others were concerned to learn that EMA approval was abruptly reversed in October 2021. 19,20 The diabetes community was reassured that this decision did not relate to safety in type 1 diabetes, but rather to manage confusion on product information interpretation of DKA risk in type 1 diabetes versus other populations, reflecting instead a possible commercial decision.…”

Section: Sglt2 Inhibitors In Type 1 Diabetes: Therapeutic and Regulat...mentioning

confidence: 99%

See 2 more Smart Citations

Sodium–glucose cotransporter 2 inhibitors in type 1 diabetes: a missed opportunity for cardiovascular protection?

Snaith

Greenfield

2022

Medical Journal of Australia

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SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study

Anson,

Zhao,

Austin

et al. 2023

Diabetologia

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Aims/hypothesis Insulin is the primary treatment for type 1 diabetes. However, alternative glucose-lowering therapies are used adjunctively, but importantly are off-label in type 1 diabetes. Little work has previously been undertaken to evaluate safety with long-term efficacy and cardio-renal benefits of such therapies. We sought to investigate the real-world impact of sodium–glucose cotransporter 2 inhibitor (SGLT2i) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy in individuals with type 1 diabetes in relation to effect on blood glucose levels, adverse events and cardio-renal outcomes. Methods We performed a retrospective cohort study of all patients aged 18 or over with type 1 diabetes on the TriNetX platform, a global collaborative network providing access to real-time, anonymised medical records. We included patients who had been treated with an SGLT2i or GLP-1 RA for at least 6 months and analysed the efficacy, safety and cardio-renal outcomes 5 years after initiation of therapy. Results We identified 196,691 individuals with type 1 diabetes, 13% of whom were treated with adjunctive glucose-lowering therapy in addition to insulin. Included in the core analysis were 1822 patients treated with a GLP-1 RA and 992 individuals treated with an SGLT2i. Both agents provided clinically meaningful reductions in HbA1c (−2.6 mmol/mol [−0.2%] with SGLT2i and −5.4 mmol/mol [−0.5%] with GLP-1 RA). The SGLT2i treated cohort showed preservation of eGFR over a 5-year period compared with the GLP-1 RA treated cohort (+3.5 ml/min per 1.73 m2 vs −7.2 ml/min per 1.73 m2, respectively), including patients with established chronic kidney disease (CKD). The SGLT2i treated cohort experienced higher rates of diabetic ketoacidosis (DKA) (RR 2.08 [95% CI 1.05, 4.12] p=0.0309) and urinary tract infection/pyelonephritis (RR 2.27 [95% CI 1.12, 4.55] p=0.019) compared with the GLP-1 RA treated cohort. However, the SGLT2i treated cohort were less likely to develop heart failure (RR 0.44 [95% CI 0.23, 0.83] p=0.0092), CKD (RR 0.49 [95% CI 0.28, 0.86] p=0.0118) and be hospitalised for any cause (RR 0.59 [95% CI 0.46, 0.76] p≤0.0001) when compared with the GLP-1 RA treated cohort. Conclusions/interpretation Both SGLT2is and GLP-1 RAs have potential benefits as adjunctive agents in type 1 diabetes. SGLT2is provide cardio-renal benefits, despite an increase in the risk of DKA and urinary tract infection compared with GLP-1 RA therapy. Long-term evaluation of the efficacy and safety of these adjunctive therapies is required to guide their use in individuals with type 1 diabetes. Graphical Abstract

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Real‐world data of 12‐month adjunct sodium‐glucose co‐transporter‐2 inhibitor treatment in type 1 diabetes from the German/Austrian DPV registry: Improved HbA1c without diabetic ketoacidosis

Cited by 17 publications

References 9 publications

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

Effects of the SGLT2 Inhibition on Cardiac Remodeling in Streptozotocin-Induced Diabetic Rats, a Model of Type 1 Diabetes Mellitus

Sodium–glucose cotransporter 2 inhibitors in type 1 diabetes: a missed opportunity for cardiovascular protection?

SGLT2i and GLP-1 RA therapy in type 1 diabetes and reno-vascular outcomes: a real-world study

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