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Effects of sodium-glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion.

ABSTRACT: Aims:The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) on fasting blood glucose concentration (FBG) in patients with unstable FBG despite undergoing intensive insulin therapy (IIT) remain unclear. This study aimed to identify the effects of SGLT2Is on unstable FBGs. Materials and methods:Thirty brittle diabetic patients with unstable FBGs despite undergoing IIT were included in the study. SGLT2Is were added and used in combination. We evaluated the data of the subjects in Evaluation 1 (immediately before using SGLT2Is) and evaluations 2, 3 and 4 (4, 24 and 48 weeks after starting concomitant therapy, respectively). FBGs were measured every day for a period of 28 days immediately before conducting Evaluations 1, 2, 3 and 4. The mean value of the 28 sets of FBG data (FBG mean) and their standard deviation (SD) values were established as each evaluation's FBGs. The changes in the mean values of the 30 subjects as well as their SD before and after concomitant therapy were evaluated. Results:The concomitant use of SGLT2Is helped reduce not only FBG mean but also SD. FBG max dropped, and the frequency of occurrence of hyperglycaemic FBG (>11.1 mmol/L) decreased. However, FBG min did not drop, and the frequency of occurrence of hypoglycaemic FBG (<3.9 mmol/L) increased. The frequency of occurrence of subjective hypoglycaemia decreased. The decrease in the SD of FBG was related to the decrease in subjective hypoglycaemia. Conclusion:Concomitant use of SGLT2Is in patients with brittle diabetes appears to be useful in terms of improvement of FBG and fewer occurrences of hypoglycaemic events.

SUBMITTER: Ogawa S

PROVIDER: S-EPMC6354752 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Effects of sodium-glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion.

Ogawa Susumu S Nako Kazuhiro K Ito Sadayoshi S

Endocrinology, diabetes & metabolism 20181201 1

<h4>Aims</h4>The effects of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) on fasting blood glucose concentration (FBG) in patients with unstable FBG despite undergoing intensive insulin therapy (IIT) remain unclear. This study aimed to identify the effects of SGLT2Is on unstable FBGs.<h4>Materials and methods</h4>Thirty brittle diabetic patients with unstable FBGs despite undergoing IIT were included in the study. SGLT2Is were added and used in combination. We evaluated the data of the sub ...[more]

PMID: 30815573

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Project description:Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower glycemia by enhancing urinary glucose excretion. The physiologic response to pharmacologically induced acute or chronic glycosuria has not been investigated in human diabetes.We evaluated 66 patients with type 2 diabetes (62 ± 7 years, BMI = 31.6 ± 4.6 kg/m(2), HbA1c = 55 ± 8 mmol/mol, mean ± SD) at baseline, after a single dose, and following 4-week treatment with empagliflozin (25 mg). At each time point, patients received a mixed meal coupled with dual-tracer glucose administration and indirect calorimetry.Both single-dose and chronic empagliflozin treatment caused glycosuria during fasting (median, 7.8 [interquartile range {IQR}, 4.4] g/3 hours and 9.2 [IQR, 5.2] g/3 hours) and after meal ingestion (median, 29.0 [IQR, 12.5] g/5 hours and 28.2 [IQR, 15.4] g/5 hours). After 3 hours of fasting, endogenous glucose production (EGP) was increased 25%, while glycemia was 0.9 ± 0.7 mmol/l lower (P < 0.0001 vs. baseline). After meal ingestion, glucose and insulin AUC decreased, whereas the glucagon response increased (all P < 0.001). While oral glucose appearance was unchanged, EGP was increased (median, 40 [IQR, 14] g and 37 [IQR, 11] g vs. 34 [IQR, 11] g, both P < 0.01). Tissue glucose disposal was reduced (median, 75 [IQR, 16] g and 70 [IQR, 21] g vs. 93 [IQR, 18] g, P < 0.0001), due to a decrease in both glucose oxidation and nonoxidative glucose disposal, with a concomitant rise in lipid oxidation after chronic administration (all P < 0.01). ? Cell glucose sensitivity increased (median, 55 [IQR, 35] pmol • min(-1) • m(-2) • mM(-1) and 55 [IQR, 39] pmol • min(-1) • m(-2) • mM(-1) vs. 44 [IQR, 32] pmol • min(-1) • m(-2) • mM(-1), P < 0.0001), and insulin sensitivity was improved. Resting energy expenditure rates and those after meal ingestion were unchanged.In patients with type 2 diabetes, empagliflozin-induced glycosuria improved ? cell function and insulin sensitivity, despite the fall in insulin secretion and tissue glucose disposal and the rise in EGP after one dose, thereby lowering fasting and postprandial glycemia. Chronic dosing shifted substrate utilization from carbohydrate to lipid. Trial registration. ClinicalTrials.Gov NCT01248364 (EudraCT no. 2010-018708-99). Funding. This study was funded by Boehringer Ingelheim.

Dataset Information

Effects of sodium-glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion.

Publications

Effects of sodium-glucose cotransporter 2 inhibitors on hypoglycaemia in brittle diabetic patients with decreased endogenous insulin secretion.

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