scholarly journals Sodium-Glucose Cotransporter 2 Inhibition and Glycemic Control in Type 1 Diabetes: Results of an 8-Week Open-Label Proof-of-Concept Trial

Diabetes Care ◽  
2014 ◽  
Vol 37 (5) ◽  
pp. 1480-1483 ◽  
Author(s):  
Bruce A. Perkins ◽  
David Z.I. Cherney ◽  
Helen Partridge ◽  
Nima Soleymanlou ◽  
Holly Tschirhart ◽  
...  
PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0141085 ◽  
Author(s):  
Bruce A. Perkins ◽  
David Z. I. Cherney ◽  
Nima Soleymanlou ◽  
Justin A. Lee ◽  
Helen Partridge ◽  
...  

Author(s):  
Lunwen Rao ◽  
Chenhong Ren ◽  
Shan Luo ◽  
Chenghu Huang ◽  
Xuefeng Li

Abstract Aims The aim was to systematically review the efficacy and safety of sodium–glucose cotransporter inhibitor (SGLT2i) as an adjunct to insulin at different follow-up durations in randomized, double-blind clinical trials in patients with type 1 diabetes. Methods We conducted a search on Medline, Embase, and the Cochrane Library for relevant studies published before May 2020. According to the duration of follow-up, the subgroup analysis included four periods: 1–4, 12–18, 24–26, and 52 weeks. In the five trials included both 24–26 and 52 weeks of follow-up, we compared the efficacy by the placebo-subtracted difference and changes in SGLT2i groups. Results Fifteen trials including 7109 participants were analyzed. The combination of SGLT2i and insulin improved hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), daily insulin dose, body weight, and blood pressure, which varied greatly by different follow-ups. Compared with %HbA1c at 24–26 weeks, placebo-subtracted differences and changes in the SGLT2i groups slightly increased. SGLT2i plus insulin treatment showed no difference in the occurrence of urinary tract infections (UTIs), hypoglycemia, or severe hypoglycemia but increased the risk of genital tract infections (GTIs) in a duration-dependent manner. SGLT2i treatment was associated with a significantly higher rate of ketone-related SAEs and diabetic ketoacidosis (DKA) at 52 weeks. Conclusion SGLT2i as an add-on therapy to insulin improved glycemic control and body weight and decreased the required dose of insulin without increasing the risk of hypoglycemia. However, after 6 months the benefits of SGLT2is on glycemic control may weaken and the risks of GTIs and DKA increased.


2008 ◽  
Vol 93 (1) ◽  
pp. 26-31 ◽  
Author(s):  
Jean Y. Park ◽  
Angeline Y. Chong ◽  
Elaine K. Cochran ◽  
David E. Kleiner ◽  
Michael J. Haller ◽  
...  

Abstract Context: Acquired generalized lipodystrophy (AGL) is marked by severe insulin resistance and hypertriglyceridemia. Rarely, AGL and type 1 diabetes (T1D) coexist. Objective: Our objective was to describe the response to leptin therapy in patients with coexisting AGL and T1D and to document the autoimmune diseases associated with AGL. Design and Setting: We conducted an open-label prospective study at the Clinical Research Center of the National Institutes of Health. Patients: Participants included 50 patients with generalized or partial lipodystrophy (acquired or congenital); two patients had both AGL and T1D. Intervention: Patients were treated with 12 months of recombinant human leptin administration to achieve high-normal serum concentrations. Results: Two patients had both AGL and T1D. The first was diagnosed with T1D at age 8 yr. Beginning at age 11 yr, he developed generalized lipodystrophy, elevated transaminases, and poor glycemic control [hemoglobin A1c (HbA1c) 10.7%] despite markedly increased insulin requirements (3.3–5 U/kg·d). Further evaluation revealed hypoleptinemia and hypertriglyceridemia. At age 15 yr, leptin therapy was initiated, and after 1 yr, his insulin requirements fell to 1 U/kg·d, his glycemic control improved (HbA1c 8.4%), and both his triglycerides and transaminases normalized. The second patient developed concurrent AGL and T1D at age 6 yr. Despite insulin doses of up to 32 U/kg·d, she developed poor glycemic control (HbA1c 10.6%), hypertriglyceridemia (2984 mg/dl), elevated transaminases, and nonalcoholic steatohepatitis. At age 13 yr, leptin therapy was started, and after 1 yr, her glycemic control improved (HbA1c 7.3%) and her insulin requirements decreased (17 U/kg·d). Her triglycerides remained elevated but were improved (441 mg/dl). Conclusions: Long-term recombinant leptin therapy is effective in treating the insulin resistance of patients with the unusual combination of T1D and AGL.


2013 ◽  
Author(s):  
P. Osborn ◽  
C. A. Berg ◽  
A. E. Hughes ◽  
P. Pham ◽  
D. J. Wiebe

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