scholarly journals Drug–Drug Interactions with Sodium-Glucose Cotransporters Type 2 (SGLT2) Inhibitors, New Oral Glucose-Lowering Agents for the Management of Type 2 Diabetes Mellitus

2014 ◽  
Vol 53 (4) ◽  
pp. 295-304 ◽  
Author(s):  
André J. Scheen
2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Tamara Young ◽  
Jing-wei Li ◽  
Amy Kang ◽  
Hiddo Heerspink ◽  
Carinna Hockham ◽  
...  

Abstract Background and Aims Patient with type 2 diabetes mellitus (T2DM) included in trials of sodium-glucose cotransporter 2 inhibitors are heterogeneous in terms of disease severity. We assessed the effects of canagliflozin compared to placebo on cardiovascular and renal outcomes in the CANVAS program according to severity of T2DM as indicated by intensity of treatment, duration of diabetes and glycaemic control. Method We compared effects on major adverse cardiovascular events ([MACE], defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) according to three indicators of T2DM severity at study baseline: number of oral glucose lowering treatments or insulin therapy (0-1, 2, 3+, insulin), duration of diabetes (<10, 10-16, >16 years) and HbA1c (<7.0, 7.0-7.5, 7.5-8.0, 8.0-8.5, 8.5-9, >9.0%). We also assessed effects on other pre-specified cardiovascular outcomes, and an adjudicated composite of end-stage kidney disease, renal death or sustained 40% decline in estimated glomerular filtration rate. We assessed for constancy of hazard ratios across subgroups by fitting an interaction term that tested for linear trend. Results Of 10,142 participants in the CANVAS Program, 1011 experienced a MACE during a mean follow-up of 3.6 years. Event rates for MACE were higher in those with longer duration of diabetes and higher HbA1c at baseline. The effect of canagliflozin on MACE in the overall population (HR 0.86, 95 % CI 0.75-0.97) was consistent irrespective of the number of glucose lowering treatments (p=0.509), duration of diabetes (p=0.174) and baseline HbA1c (p =0.314). Effects were also consistent across different levels of T2DM disease severity for all other outcomes studied. Conclusion Higher event rates were observed in those with longer disease duration and higher HbA1c. The proportional risk reductions achieved with canagliflozin were comparable regardless of diabetes duration, number of therapies or HbA1C at baseline.


Gut ◽  
2019 ◽  
Vol 69 (2) ◽  
pp. 295-303 ◽  
Author(s):  
Annieke C G van Baar ◽  
Frits Holleman ◽  
Laurent Crenier ◽  
Rehan Haidry ◽  
Cormac Magee ◽  
...  

BackgroundThe duodenum has become a metabolic treatment target through bariatric surgery learnings and the specific observation that bypassing, excluding or altering duodenal nutrient exposure elicits favourable metabolic changes. Duodenal mucosal resurfacing (DMR) is a novel endoscopic procedure that has been shown to improve glycaemic control in people with type 2 diabetes mellitus (T2D) irrespective of body mass index (BMI) changes. DMR involves catheter-based circumferential mucosal lifting followed by hydrothermal ablation of duodenal mucosa. This multicentre study evaluates safety and feasibility of DMR and its effect on glycaemia at 24 weeks and 12 months.MethodsInternational multicentre, open-label study. Patients (BMI 24–40) with T2D (HbA1c 59–86 mmol/mol (7.5%–10.0%)) on stable oral glucose-lowering medication underwent DMR. Glucose-lowering medication was kept stable for at least 24 weeks post DMR. During follow-up, HbA1c, fasting plasma glucose (FPG), weight, hepatic transaminases, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), adverse events (AEs) and treatment satisfaction were determined and analysed using repeated measures analysis of variance with Bonferroni correction.ResultsForty-six patients were included of whom 37 (80%) underwent complete DMR and 36 were finally analysed; in remaining patients, mainly technical issues were observed. Twenty-four patients had at least one AE (52%) related to DMR. Of these, 81% were mild. One SAE and no unanticipated AEs were reported. Twenty-four weeks post DMR (n=36), HbA1c (−10±2 mmol/mol (−0.9%±0.2%), p<0.001), FPG (−1.7±0.5 mmol/L, p<0.001) and HOMA-IR improved (−2.9±1.1, p<0.001), weight was modestly reduced (−2.5±0.6 kg, p<0.001) and hepatic transaminase levels decreased. Effects were sustained at 12 months. Change in HbA1c did not correlate with modest weight loss. Diabetes treatment satisfaction scores improved significantly.ConclusionsIn this multicentre study, DMR was found to be a feasible and safe endoscopic procedure that elicited durable glycaemic improvement in suboptimally controlled T2D patients using oral glucose-lowering medication irrespective of weight loss. Effects on the liver are examined further.Trial registration numberNCT02413567


2019 ◽  
Vol 22 (3) ◽  
pp. 206-216
Author(s):  
Inna V. Misnikova ◽  
Yulia A. Kovaleva ◽  
Mikhail А. Isakov ◽  
Alexander V. Dreval

BACKGROUND: Data of real clinical practice in diabetes mellitus (DM) register allow to evaluate features and trends in structure of glucose-lowering therapy (GLT). AIM: Тo analyze of structure of GLT received by patients with type 2 diabetes mellitus (T2DM) in Moscow region for 2018 and to evaluate its dynamics over 15 years. METHODS: Analysis of GLT structure was carried out on basis of data from register of patients with DM in Moscow region, which is part of National register of diabetes mellitus in Russian Federation. In March 2018 it contained data on 211,792 T2DM patients of Moscow region. Structure of GLT administration was evaluated according T2DM duration, patients age and presence of cardiovascular diseases (CVD). Dynamics of GLT is analyzed from 2004 to 2018 yrs. RESULTS: In 2018 non-insulin glucose-lowering drugs (NIGD) prescription prevailed (78.3%), insulin therapy was prescribed in 18.5% of patients, 3.2% of patients did not receive drug therapy. Most commonly prescribed NIGD were metformin (69.3%) and sulfonylurea (51.3%). Older patients more often than younger did not use GLT at all and less frequently received insulin therapy and iDPP-4. Insulin therapy was prescribed twice as often in patients with CVD compared with patients without CVD (29.6% and 15.5%). NIGD monotherapy has been less commonly used in patients with CVD (67.3% and 81.2%). Glucagon-like peptide-1 receptor agonists (GLP-1 RA) were prescribed to patients with CVD GLP-1 RA in 0.1% of cases, without CVD in 0.3% of cases, and sodium-glucose cotransporter 2 (SGLT2) inhibitors in 1.1% and 0.6%. correspondently. CONCLUSION: Metformin was most commonly prescribed drug in GLT structure for T2DM patients in the Moscow region in 2018 yr. Percentage of new drugs in the structure of GLT increased mainly due to iDPP-4, and secondly due to SGLT2 inhibitors. New classes of GLT were more often prescribed to patients of younger age, with diabetes duration up to 10 years, overweight or obese. Administration of NIGD with proven cardiovascular protection in presence of CVD is almost two times less than for those without CVD.


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A467-A467
Author(s):  
Muhammad Saleem ◽  
Nanik Ram ◽  
Sajjad Ali Khan ◽  
Zafar Aleem Suchal ◽  
Muhammad Mustansir Mehdi Khan

Abstract Background: SGLT-2 inhibitors are a group of oral medications that work independently of insulin working as anti-diabetics by enhancing the excretion of glucose. The purpose of our study was to assess the improvement in terms of HbA1c, weight, blood pressure and BMI and the hepatics and renal effect in terms of SGPT and Creatinine in patients already on three oral glucose lowering agents when SGLT-2 inhibitor was added to their medications. Methods: This retrospective, real world, single center study included 99 patients (mean age [Standard Deviation]: 53.8 [9.63] years) with poorly control type 2 diabetes. Data was recorded at three times, before the addition of SGLT-2 inhibitor and then at 3 and 6 month follow up after the drug had been added in patient’s medications. Physical parameters namely weight, BMI and blood pressure were recorded in the clinic while HbA1c, SGPT and Creatinine were checked by laboratory. Results: Improvement was seen in all parameters at both 3 and 6 month follow up interval. The reduction in HbA1c was statistically significant (P-value &lt; 0.001) with (Mean Reduction [Standard Deviation)) 0.81[1.02] % at 3 months and 1.07[1.11] % at 6 months. Weight was also significantly reduced (P-value &lt; 0.001) with (MR [SD]) 1.83[2.32] kg at 3 and 4.02[6.04] kg at 6 months. Statistically significant reduction (P-value &lt; 0.001) in BMI was also seen with 0.69[0.95] kgm-2 at 3 months and 2.13[3.41] kgm-2 at 6 months of follow up. The systolic blood pressure showed significant reduction (P-value &lt; 0.05) of 5.9[15.76] mmHg at 3 months and 6.37[18.33] mmHg at 6 months. The creatinine and SGPT values of the patient showed minimal variation over the course of these 6 months of follow up. Conclusion: Our study showed that SGPT-2 can be reliably used in patients in which diabetes is not being controlled by other glucose lowering agents and is safe for use in patients in which hepatic and renal function needs to be preserved. Keywords: SGLT-2 inhibitors, Type 2 Diabetes Mellitus, Pakistan


Author(s):  
Elias A Sanidas ◽  
Dimitrios P Papadopoulos ◽  
Erifili Hatziagelaki ◽  
Charalampos Grassos ◽  
Maria Velliou ◽  
...  

Abstract Sodium glucose cotransporter 2 (SGLT2) inhibitors represent a novel class of oral antihyperglycemic drugs that have been approved over the last decade for the management of type 2 diabetes mellitus. Except the glucose-lowering effects, robust evidence also suggests that SGLT2 inhibitors confer benefits in cardiovascular system. The purpose of this review was to investigate the effects of SGLT2 inhibitors across the spectrum of arterial hypertension.


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