SGLT-2 Inhibitors - A Systematic Review of their Extra-Glycaemic Benefits and Safety Profile

BACKGROUND Type 2 Diabetes mellitus is a major cause of mortality due to its complications such as cardiovascular disease (CVD), stroke and end stage renal disease (ESRD). Sodium Glucose Co-Transporter-2 inhibitors is a new class of oral hypoglycaemics which impart additional benefits primarily on heart and kidney. The most commonly used drugs in this class include Canagliflozin, Dapagliflozin and Empagliflozin. However, these drugs are associated with certain adverse effects. This review aims to appraise the extra-glycaemic benefits and adverse effect profile of SGLT-2 inhibitors so as to minimize the morbidity and mortality associated with type 2 diabetes mellitus. METHODS Thorough literature search was made using search engines like PubMed, Cochrane library, Medline and Google scholar to retrieve articles pertaining to extra glycaemic benefits and adverse effects of SGLT2i. RESULTS Majority of studies like CANVAS, EMPA-REG and DECLARE-TIMI done on Canagliflozin, Empagliflozin and Dapagliflozin respectively have concluded that these drugs possess additional benefits like reduced risk of heart failure, positive effects on kidney functions, favourable effects on body weight, reduced levels of uric acid and reduction in blood pressure. However, these drugs are associated with certain adverse effects like increased risk of genital and urinary tract infection. CONCLUSIONS The extra-glycaemic benefits of SGLT2i on heart, kidney and other parameters like body weight, uric acid and blood pressure have been proven by a number of studies conducted over several years. Nevertheless, these drugs are associated with certain adverse effects like increased risk of genital and urinary tract infection which can be mitigated by maintaining hydration, perineal hygiene and educating the patient. KEYWORDS Sodium Glucose Co-Transporter-2 Inhibitors, Type 2 Diabetes mellitus, Canagliflozin, Dapagliflozin, Empagliflozin, Extra Glycaemic Effects, Adverse effects

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Efficacy and Safety of Ertugliflozin in Patients With Type 2 Diabetes Mellitus and Established Cardiovascular Disease Treated With Metformin and Sulfonylurea

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.676 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A331-A331

Author(s):

Matthew J Budoff ◽

Timothy M E Davis ◽

Alexandra G Palmer ◽

Robert Frederich ◽

David E Lawrence ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Cardiovascular Disease ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

Glycemic Control ◽

Sglt2 Inhibitor ◽

Efficacy And Safety

Abstract Introduction: Ertugliflozin (ERTU), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, is approved as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus (T2DM). Aim: As a pre-specified sub-study of the Phase 3 VERTIS CV trial (NCT01986881), the efficacy and safety of ERTU were assessed in patients with T2DM and established atherosclerotic cardiovascular disease (ASCVD) inadequately controlled with metformin and sulfonylurea (SU). Methods: Patients with T2DM, established ASCVD, and HbA1c 7.0–10.5% on stable metformin (≥1500 mg/day) and SU doses as defined per protocol were randomized to once-daily ERTU (5 mg or 15 mg) or placebo. The primary sub-study objectives were to assess the effect of ERTU on HbA1c compared with placebo and to evaluate safety and tolerability during 18-week follow-up. Key secondary endpoints included proportion of patients achieving HbA1c <7%, fasting plasma glucose (FPG), body weight, and systolic blood pressure. Changes from baseline at Week 18 for continuous efficacy endpoints were assessed using a constrained longitudinal data analysis model. Results: Of the 8246 patients enrolled in the VERTIS CV trial, 330 patients were eligible for this sub-study (ERTU 5 mg, n=100; ERTU 15 mg, n=113; placebo, n=117). Patients had a mean (SD) age of 63.2 (8.4) years, T2DM duration 11.4 (7.4) years, estimated glomerular filtration rate 83.5 (17.8) mL/min/1.73 m2, and HbA1c 8.3% (1.0) (67.4 [10.6] mmol/mol). At Week 18, ERTU 5 mg and 15 mg were each associated with a significantly greater least squares mean (95% CI) HbA1c reduction from baseline versus placebo; the placebo-adjusted differences for ERTU 5 mg and 15 mg were –0.7% (–0.9, –0.4) and –0.8% (–1.0, –0.5), respectively (P<0.001). A higher proportion of patients in each ERTU group achieved HbA1c <7% relative to placebo (P<0.001). ERTU significantly reduced FPG and body weight (P<0.001, for each dose versus placebo), but not systolic blood pressure. Adverse events were reported in 48.0%, 54.9%, and 47.0% of patients in the ERTU 5 mg, 15 mg, and placebo groups, respectively. Genital mycotic infections were experienced by significantly higher proportions of male patients who received ERTU 5 mg and 15 mg (4.2% and 4.8%, respectively) versus placebo (0.0%; P≤0.05) and by a numerically, but not significantly, higher proportion of female patients who received ERTU 15 mg (10.3%) compared with placebo (3.8%) (P=0.36). The incidences of symptomatic hypoglycemia were 11.0% (5 mg), 12.4% (15 mg), and 7.7% (placebo), and of severe hypoglycemia 2.0% (5 mg), 1.8% (15 mg), and 0.9% (placebo). Conclusion: Among patients with T2DM and ASCVD, ERTU (5 mg and 15 mg) added to metformin and SU for 18 weeks improved glycemic control (HbA1c and FPG) and reduced body weight, and was generally well tolerated with a safety profile consistent with the SGLT2 inhibitor class.

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Comparative Study of Level of Serum Uric Acid in Type 2 Diabetes Mellitus Associated with Hypertension

Anwer Khan Modern Medical College Journal ◽

10.3329/akmmcj.v9i2.39202 ◽

2018 ◽

Vol 9 (2) ◽

pp. 96-101

Author(s):

Roksana Yeasmin ◽

MA Muttalib ◽

Nazneen Sultana ◽

Md Jamil Hasan Karami ◽

Ayatunnessa ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Serum Uric Acid ◽

Exercise Time ◽

The Mean ◽

And Control

Background: The role of uric acid in the progression of prediabetes to diabetes has been known. Serum uric acid has been shown to beassociated with cardiovascular disease, hypertension, and chronic kidney disease. However, conflicting data exist asregards the serum uric acid (UA) levels in type 2 diabetes mellitus, which are associated with risk factors andcomplications.Material & Methods: The present study was designed to look for any association of serum uric acid with hypertension in type 2diabetes mellitus, taking into consideration the relevant clinical, biochemical and the anthropometric data. 110 patientswith type 2 male diabetes mellitus as case and 100 healthy malecontrols were included in this study.Results: This study shows that there were significant differences in mean of age, duration of DM, exercise time, waist hip ratio, systolic blood pressure and diastolic blood pressure within case and control but no significant differences of mean BMI was found between and control. The mean age, duration of DM, exercise time, waist hip ratio, systolic blood pressure and diastolic blood pressure and BMI were (51.83±9.911 years, 6.87±5.54 years, 1.94±.831 hours, .92±.03, 140±6.75 mm of Hg,90±2.41 mm of Hg and 25.43±3.19 Kg/m2 respectively), where as in controls these were (44.81±9.66 yrs, 00 years, 1.12±.327 hours, .91±.03, 130±1.28 mm of Hg, 80±6.18 mm of Hg and 24.96±3.02 Kg/m2 respectively). This table also shows that significant differences in mean of FBS, ABF, HbA1C and S. Uric acid between case and control, but there was no significant differences of mean TG, Cholesterol, HDL and LDL. The mean of FBS, ABF, HbA1C and S. Uric acid among the cases were (8.19±2.48 mmol/L, 11.29±3.47 mmol/L, 7.96±6.04 mg%, 189.72±111.36 mg/dl, 179±43 mg/dl, 38.38±13.77 mg/dl, 102.10±35.79 mg/dl and 8.39±2.61 mg/dl respectively, on the other hand among the control these were 5.91±1.13 mmol/L, 9.19±1.95 mmol/L, 5.93±1.01 mg%, 200±104.49 mg/dl, 183±42.25 mg/dl, 38.14±5.52 mg/dl, 110±33.23 mg/dl and 5.14±.84 mg/dl respectively.Anwer Khan Modern Medical College Journal Vol. 9, No. 2: Jul 2018, P 96-101

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The Association of Uric Acid Calculi with Obesity, Prediabetes, Type 2 Diabetes Mellitus, and Hypertension

BioMed Research International ◽

10.1155/2017/7523960 ◽

2017 ◽

Vol 2017 ◽

pp. 1-6 ◽

Cited By ~ 6

Author(s):

Fang-Yeh Chu ◽

Chih-Chun Chang ◽

Pin-Hao Huang ◽

Yi-Ning Lin ◽

Po-Wen Ku ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Urinary Tract Infection ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Surgical Management ◽

Surgical Intervention ◽

Statistical Significance ◽

Urinary Calculi

Objectives.To disclose the link between the composition of urolithiasis, especially that of uric acid calculi, and obesity, prediabetes, type 2 diabetes mellitus, and hypertension.Materials and Methods.Patients who had urinary calculi and underwent surgical treatment were registered in the study. The composition of urinary calculi was analyzed and correlated with clinical features and biomedical profiles of the patients before surgical intervention.Results.A total of 666 patients with urolithiasis who underwent surgical management were registered and analyzed. In those who had uric acid calculi, there was a significant association with prediabetic (OR: 20.11, 95% CI: 7.40–54.63,P<0.001) and diabetic states (OR: 11.55, 95% CI: 4.41–29.97,P<0.001). It also seemed that uric acid calculi were related to obesity but there was no statistical significance (OR: 2.45, 95% CI: 0.91–6.62,P=0.078). There was no association of uric acid calculi with hypertension (OR: 1.08, 95% CI: 0.54–2.17,P=0.822) and concurrent urinary tract infection (OR: 0.93, 95% CI: 0.44–1.96,P=0.841).Conclusion.There was a remarkable association of uric acid calculi with prediabetic and diabetic states. The uric acid calculi were also seemingly associated with obesity in patients with urolithiasis undergoing surgical management.

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Association of serum creatinine levels and risk of type 2 diabetes mellitus in Korea: a case control study

BMC Endocrine Disorders ◽

10.1186/s12902-021-00915-2 ◽

2022 ◽

Vol 22 (1) ◽

Author(s):

Do Kyeong Song ◽

Young Sun Hong ◽

Yeon-Ah Sung ◽

Hyejin Lee

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Skeletal Muscle ◽

Type 2 Diabetes Mellitus ◽

Serum Creatinine ◽

Plasma Glucose ◽

Fasting Plasma Glucose ◽

Increased Risk

Abstract Background Reduced skeletal muscle has been suggested as a potential risk factor for type 2 diabetes mellitus (T2DM). Serum creatinine is the primary metabolite of creatine in skeletal muscle. Therefore, low serum creatinine levels may be associated with an increased risk of T2DM. We aimed to evaluate the association between serum creatinine levels and the risk of T2DM in Korea. Methods We analyzed a total of 264,832 nondiabetic adults older than 40 years of age who had undergone a national health examination at least once from 2009 to 2015 in the Korean National Health Insurance Service Cohort. Hazard ratios for T2DM were calculated. Results In men, serum creatinine levels and the risk for T2DM showed an inverse J-shaped association. This association was confirmed after adjustment for age, body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), and fasting plasma glucose. In women, there was a trend that serum creatinine levels were inversely associated with the risk of T2DM among those with serum creatinine below 1.1 mg/dl. However, serum creatinine levels were not significantly associated with the risk of T2DM after adjustment for age, BMI, SBP, DBP, and fasting plasma glucose. Conclusions Reduced levels of serum creatinine were significantly associated with an increased risk of T2DM in men with creatinine below 1.20 mg/dl. There was a trend that decreased levels of serum creatinine were associated with an increased risk of T2DM among women with serum creatinine below 1.1 mg/dl, although this result was not statistically significant.

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High Bodyweight Variability Increases Depression Risk in Patients With Type 2 Diabetes Mellitus: A Nationwide Cohort Study in Korea

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.765129 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ji Hyun An ◽

Kyung-do Han ◽

Jin-Hyung Jung ◽

Juhwan Yoo ◽

Maurizio Fava ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

Obese Patients ◽

Type 2 Dm ◽

Increased Risk ◽

Quartile Group ◽

New Onset

Objectives: Although obesity is associated with increased risk for depression in patients with type 2 diabetes mellitus (DM), the relationship between body weight variability (BWV) and depression remains poorly studied. This study was to investigate the incidence of depression in patients with type 2 DM according to their BWV.Methods: Intraindividual variation in body weight were measured in the nationwide, population-based retrospective cohort of 540,293 patients with type 2 DM from the Korean national health insurance system between 2009 and 2010. The diagnoses of new-onset depression occurring until the end of 2017 were ascertained. Risk of new-onset depression was examined using multivariate-adjusted Cox proportional hazards regression analysis by BWV quartile.Results: 93,149 (17.2%) patients developed new-onset depression for the follow up. BWV was significantly associated with an increased risk of depression after adjusting for confounding factors. The highest BWV quartile group had a hazard ratio (HR) of 1.17 (95% CI 1.15–1.19) compared to the lowest BWV quartile group as a reference. Obese patients in the highest BWV quartile group showed 12% increased risk of depression (HR 1.12, 95% CI 1.09–1.15) while non-obese patients in the highest BWV quartile group showed 20% increased risk of depression (HR: 1.20, 95% CI: 1.17–1.23) compared to their respective lowest BWV quartile groups.Conclusion: A higher BWV was significantly associated with an increased risk of depression in patients with type 2 DM. Thus, BWV may serve as an indicator for early detection of depression in type 2 DM patients.

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Association between uric acid level and incidence of macroalbuminuria in people with type 2 diabetes mellitus: A 4.5-year cohort study

10.21203/rs.2.18350/v1 ◽

2019 ◽

Author(s):

Yun-Ju Lai ◽

Yu-Yen Chen ◽

Li-Jung Chen ◽

Po-Wen Ku ◽

Kuo-Chuan Hung ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Serum Uric Acid ◽

Cox Regression ◽

Characteristic Curve ◽

Cox Regression Analysis ◽

Increased Risk

Abstract Background: Using animal models and molecular biology researches, hyperuricemia has been shown to instruct renal arteriolopathy, arterial hypertension, and microvascular injury involving the renin-angiotensin system and resulting in renal function impairment. Nevertheless, the association between uric acid levels and the development of macroalbuminuria has been under-investigated in people with type 2 diabetes mellitus. Methods: Patients with type 2 diabetes and regular outpatient visits were recruited from a community hospital in Taiwan since January 2014. Demographics, lifestyle features, and medical history were gathered by well-trained interviewers. All participants underwent comprehensive physical examinations, including a biochemical assay of venous blood specimens and urine samples after an 8-hour overnight fast. Participants were followed until June 2018. The primary outcome was the macroalbuminuria incidence. Univariable and multivariable Cox regression analysis were employed to explore the relation between uric acid and incident macroalbuminuria. Uric acid cutoffs for incident macroalbuminuria were determined with the receiver operator characteristic curve. Results: We included 247 qualified subjects (mean age: 64.78 years old [standard deviation=11.29 years]; 138 [55.87%] men). During a 4.5-year follow-up duration, 20 subjects with incident macroalbuminuria were recognized. Serum uric acid was significantly associated with an increased risk of incident macroalbuminuria (adjusted hazard ratio=2.39; 95% confidence interval: 1.53-3.75; p<0.001) with potential confounders adjustment. The uric acid cutoff point was 6.9 mg/dL (area under the curve 0.708, sensitivity 60.0%, specificity 84.58%) for incident macroalbuminuria. Conclusions: Serum uric acid was associated with incident macroalbuminuria among people with type 2 diabetes.

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Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan

PeerJ ◽

10.7717/peerj.9998 ◽

2020 ◽

Vol 8 ◽

pp. e9998

Author(s):

Jung-Fu Chen ◽

Yun-Shing Peng ◽

Chung-Sen Chen ◽

Chin-Hsiao Tseng ◽

Pei-Chi Chen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Weight Loss ◽

Type 2 Diabetes Mellitus ◽

Logistic Regression ◽

Body Weight ◽

Retrospective Study ◽

Multivariate Logistic Regression

Aims/Introduction To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. Materials and Methods In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. Results A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by −0.73% (95% confidence interval [CI] −0.80, −0.67), body weight was -1.61 kg (95% CI −1.79, −1.42), and systolic/diastolic blood pressure by −3.6/−1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (−0.82%) than switched therapy (−0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. Conclusions In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

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EFFECTS OF LONG-TERM ROUX-EN-Y GASTRIC BYPASS ON BODY WEIGHT AND CLINICAL METABOLIC COMORBIDITIES IN BARIATRIC SURGERY SERVICE OF A UNIVERSITY HOSPITAL

ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) ◽

10.1590/0102-6720201600s10006 ◽

2016 ◽

Vol 29 (suppl 1) ◽

pp. 20-23 ◽

Cited By ~ 6

Author(s):

Cátia Ferreira da SILVA ◽

Larissa COHEN ◽

Luciana d'Abreu SARMENTO ◽

Felipe Monnerat Marino ROSA ◽

Eliane Lopes ROSADO ◽

...

Keyword(s):

Diabetes Mellitus ◽

Blood Pressure ◽

Type 2 Diabetes ◽

Bariatric Surgery ◽

Gastric Bypass ◽

Type 2 Diabetes Mellitus ◽

Body Weight ◽

High Blood Pressure

ABSTRACT Background: Due to the high failure rate observed in the clinical treatment of morbid obesity an increase in bariatric surgery indications, as an alternative for the control of obesity and comorbidities, is noticeable. Aim: To evaluate the performance of type 2 diabetes mellitus, high blood pressure and dyslipidemia in patients submitted to Roux-en-Y gastric bypass in late follow-up. Methods: Retrospective analysis of 59 patients included in the bariatric surgery program. Anthropometric (height and body weight) and laboratory (LDLc, HDLc, VLDLc, triglyceride -TG - and glucose) data were collected on pre- and postoperative stages, through medical records. Results: Among the patients, 86% were female aged 43±11, of whom 52% had attended high school. The average postoperative time was 7±3 years. During the postoperative period, there were decreases of weight and body mass index, respectively (133±06 kg vs 91±04 kg p<0.05 e 49±74 kg/m2 vs 33±79 kg/m2, p<0.05). In comparison to the preoperative stage, lower concentrations of glucose (101.00±26.99 vs 89,11±15.19, p=0.014), total cholesterol rates (179.00±37,95 vs 167.48±28,50, p=0.016), LDLc (104.30±33.12 vs 91.46±24.58, p=0.016), VLDLc (25.40±11,12 vs 15.68±7.40, p<0.01), and TG (143.35±86.35 vs 82.45±37.39, p<0.01) and higher concentrations of HDLc (43.53±8.23 vs 57.90±15.60, p<0.01) were identified in the postoperative stage. 40% of hypertensive patients were still undergoing high blood pressure treatment during the postoperative stage. There was remission of type 2 diabetes mellitus and dyslipidemia on 81% and 94% of the cases, respectively. Conclusion: Roux-en-Y gastric bypass has proven itself to be an effective long term procedure, promoting weight loss, remission of DM2 and dyslipidemia.

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