scholarly journals Cardio-renal protective effects of SGLT2 inhibitors in patients with type 2 diabetes mellitus and severely impaired renal function

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
M Kanai ◽  
K Kimura ◽  
H Motoki ◽  
S Suzuki ◽  
T Okano ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Impaired Renal Function ◽  
Sglt2 Inhibitors ◽  
Protective Effects ◽  
Primary Endpoints ◽  
Group A ◽  
Severe Renal Dysfunction ◽  
Group B

Abstract Background Prognostic impact of Sodium-Glucose Cotransporter 2 (SGLT2) inhibitors on cardiovascular and renal outcome was unknown in patients with type-2 diabetes mellitus (DM) and severely impaired renal function. Methods From July 2015 to December 2020, patients with type-2 DM who were taken SGLT2 inhibitors for more than six months were retrospectively screened. Patients with estimated glomerular filtration rate (eGFR) over 60ml/min/1.73m2 were excluded. We divided those patients into two groups by eGFR; less than 45ml/min/1,73m2 were group A and 46–60ml/min/m2 were group B. Randomly selected patients with DM not taking SGLT2 inhibitors and having severe renal dysfunction: eGFR less than 45ml/min/m2 (Group C) were set as controls. The primary outcome was a composite of cardiovascular/renal death, initiation of dialysis, doubling of the serum creatine level, decline in the eGFR more than 30%, nonfatal myocardial infraction, nonfatal stroke, and hospitalization for heart failure. Results Totally 418 patients were enrolled. Median age was 71 years (group A, n=106), 64 years (group B, n=115), and 77 years (group C, n=201) (p<0.001). After median 24 months follow-up, primary endpoints were observed 24.5% in group A, 4.3% in group B, 36.8% in group C (p<0.001). In Kaplan-Meier analysis, significantly lower incidence of primary endpoints were observed in SGLT2 groups (group A and B) than controls (p<0.001, Figure 1). In patients with severe renal dysfunction, taking SGLT2 inhibitors tended to decrease future renal event (Figure 2). The incidence of SGLT2 related adverse events was not different between 2 groups (A and B). Conclusions Even in patients with severe renal dysfunction, SGLT2 inhibitors would have cardio-renal protective effects without drug-related adverse effects. FUNDunding Acknowledgement Type of funding sources: None.

Mechanisms of Protective Effects of SGLT2 Inhibitors in Cardiovascular Disease and Renal Dysfunction

2019 ◽  
Vol 19 (20) ◽  
pp. 1818-1849 ◽  
Author(s):  
Ban Liu ◽  
Yuliang Wang ◽  
Yangyang Zhang ◽  
Biao Yan
Keyword(s):  
Diabetes Mellitus ◽  
Heart Failure ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renal Dysfunction ◽  
Sglt2 Inhibitors ◽  
Sodium Glucose Cotransporter ◽  
Glucose Reabsorption ◽  
Renal Glucose Reabsorption

: Type 2 diabetes mellitus is one of the most common forms of the disease worldwide. Hyperglycemia and insulin resistance play key roles in type 2 diabetes mellitus. Renal glucose reabsorption is an essential feature in glycaemic control. Kidneys filter 160 g of glucose daily in healthy subjects under euglycaemic conditions. The expanding epidemic of diabetes leads to a prevalence of diabetes-related cardiovascular disorders, in particular, heart failure and renal dysfunction. Cellular glucose uptake is a fundamental process for homeostasis, growth, and metabolism. In humans, three families of glucose transporters have been identified, including the glucose facilitators GLUTs, the sodium-glucose cotransporter SGLTs, and the recently identified SWEETs. Structures of the major isoforms of all three families were studied. Sodium-glucose cotransporter (SGLT2) provides most of the capacity for renal glucose reabsorption in the early proximal tubule. A number of cardiovascular outcome trials in patients with type 2 diabetes have been studied with SGLT2 inhibitors reducing cardiovascular morbidity and mortality. : The current review article summarises these aspects and discusses possible mechanisms with SGLT2 inhibitors in protecting heart failure and renal dysfunction in diabetic patients. Through glucosuria, SGLT2 inhibitors reduce body weight and body fat, and shift substrate utilisation from carbohydrates to lipids and, possibly, ketone bodies. These pleiotropic effects of SGLT2 inhibitors are likely to have contributed to the results of the EMPA-REG OUTCOME trial in which the SGLT2 inhibitor, empagliflozin, slowed down the progression of chronic kidney disease and reduced major adverse cardiovascular events in high-risk individuals with type 2 diabetes. This review discusses the role of SGLT2 in the physiology and pathophysiology of renal glucose reabsorption and outlines the unexpected logic of inhibiting SGLT2 in the diabetic kidney.

scholarly journals Dipeptidyl peptidase-4 inhibitor (teneligliptin) significantly reduces liver fat content and delays progression of non-alcoholic steatohepatitis in type 2 diabetes mellitus patients

2021 ◽  
Vol 8 (12) ◽  
pp. 1817
Author(s):  
Vishal Kumar Gupta ◽  
Richa Giri ◽  
Saurabh Agrawal
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Dipeptidyl Peptidase ◽  
Liver Fat ◽  
Liver Fat Content ◽  
Group A ◽  
The Mean ◽  
Group B

Background: Dipeptidyl peptidase (DPP)-4 inhibitors, anti-diabetic agents, are expected to be effective for treatment of non-alcoholic fatty liver disease (NAFLD). Several studies have shown that some DPP-4 inhibitors alleviate hepatic steatosis or steatohepatitis in type 2 diabetic mice or rats. Teneligliptin is DPP4 inhibitor whose efficacy to control blood sugar is well established but its effect on liver is not studied well. In present study we investigated effect of teneligliptin, a DPP-4 inhibitor on patients of type 2 diabetes with non-alcoholic steatohepatitis (NASH). Methods: This was a randomized, double-blind study in which 64 patients between ages of 18 to 80 years were selected for study. Participants were identified as type 2 diabetes with biopsy confirmed NASH. We excluded the patients with glucocorticoid use, hepatitis B or C, and other diseases that might affect liver function. Results: The mean HbA1c change after 48 weeks of therapy in group A was-1.06 % and in group B was-0.77% and this was statistically insignificant (p>0.06). The mean AST change after 48 weeks of therapy in group A was-45.4% and in group B was-33.3% and this was statistically significant (p<0.001). The mean ALT change after 48 weeks of therapy in group A was-41.6% and in group B was-22.7% and this was statistically significant (p<0.001). The change in liver fat content (LFC) after 48 weeks of therapy in group A was-15.4% and group B was-7.14% and this was also statistically significant (p<0.001).Conclusions: Result of our study revealed that teneligliptin significantly reduce serum transaminases in patients of NASH with type 2 DM. Teneligliptin significantly reduce LFC and delay progression of NASH independent of diabetes control in type 2 diabetes mellitus (DM) patients. These data show significant antisteatotic and anti-inflammatory effect of teneligliptin in type 2 diabetes patients.

scholarly journals Treatment Compliance with Fixed-Dose Combination of Vildagliptin/Metformin in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Metformin Monotherapy: A 24-Week Observational Study

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Grigorios Rombopoulos ◽  
Magdalini Hatzikou ◽  
Athanasios Athanasiadis ◽  
Moyses Elisaf
Keyword(s):  
Diabetes Mellitus ◽  
Treatment Compliance ◽  
Fixed Dose Combination ◽  
Fixed Dose ◽  
Combination Group ◽  
Metformin Monotherapy ◽  
Group A ◽  
Dose Combination ◽  
Group B

Objective. To evaluate the differences in treatment compliance with vildagliptin/metformin fixed-dose versus free-dose combination therapy in patients with type 2 diabetes mellitus (T2DM) in Greece.Design. Adult patients with T2DM, inadequately controlled with metformin monotherapy, (850 mg bid), participated in this 24-week, multicenter, observational study. Patients were enrolled in two cohorts: vildagliptin/metformin fixed-dose combination (group A) and vildagliptin metformin free-dose combination (group B).Results. 659 patients were enrolled, 360 were male, with mean BMI 30.1, mean T2DM duration 59.6 months, and mean HbA1c at baseline 8%; 366 patients were assigned to group A and 293 to group B; data for 3 patients was missing. In group A, 98.9% of patients were compliant with their treatment compared to 84.6% of group B. The odds ratio for compliance in group A versus B was (OR) 18.9 (95% CI: 6.2, 57.7;P<0.001). In group A mean HbA1c decreased from 8.1% at baseline to 6.9% (P<0.001) at the study end and from 7.9% to 6.8% (P<0.001) in group B.Conclusions. Patients in group A were more compliant than patients in group B. These results are in accordance with international literature suggesting that fixed-dose combination therapies lead to increased compliance to treatment.

Combined Bendamustine, Prednisone and Bortezomib (BPV) In Patients With Relapsed Or Refractory Multiple Myeloma and Light Chain Induced Renal Failure

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3203-3203 ◽  
Author(s):  
Wolfram Pönisch ◽  
Barbara Moll ◽  
Dietger Niederwieser
Keyword(s):  
Multiple Myeloma ◽  
Renal Failure ◽  
Renal Dysfunction ◽  
Light Chain ◽  
Severe Side Effect ◽  
Renal Response ◽  
Group A ◽  
Severe Renal Dysfunction ◽  
Grade 3 ◽  
Group B

Abstract Introduction Serious renal failure represents a main complication of Multiple Myeloma (MM). An estimated 25% to 50% of patients are affected during the course of their disease. These patients are at increased risk for infections and have a significantly worse prognosis. Small phase I/II studies suggest that treatment with chemotherapy and/or new substances results in recovery of renal function in more than 25%. The window of opportunity for reversal of renal impairment is rather small making an immediate and highly active treatment strategy mandatory. Bortezomib and bendamustine have turned out to be quickly acting and effective drugs in the treatment of MM. Methods Between March 2005 and March 2013, 36 patients (median age 64; range 32-81 years) with relapsed/refractory MM and light chain induced renal failure (creatinine clearance <60ml/min) were treated with bendamustine 60mg/qm on day 1 and 2, bortezomib 1.3mg/qm on day 1, 4, 8 and 11, and prednisone 100mg on day 1, 2, 4, 8 and 11. Cycles were repeated every 21 days. Patients were divided into two groups: group A (n=20) consisted of patients with moderate or severe renal dysfunction (eGFR 15-59ml/min) and group B (n=16) of patients with renal failure/dialysis (eGFR <15ml/min). Results The median number of the BPV-treatment was 2 (1-7) cycles. 24 patients (67%) responded after at least one cycle of chemotherapy with 3 CR, 3 nCR, 6 VGPR, and 12 PR. Six patients had MR, 2 patients stable disease and 4 patients had a progress. With a median follow up of 22 months of the surviving patients, median PFS and OS for patients with moderate or severe renal dysfunction (group A) were 10 months and 25 months, respectively. Outcome for these patients was significantly better compared to patients with renal failure/dialysis (group B) with a median PFS and OS of 3 months and 7 months, respectively (p<0.02). Eleven patients showed a CRrenal, 5 patients a PRrenal and 15 patients a MRrenal. Median time to first renal response and best renal response were 21 days and 42 days, respectively. The most common severe side effect was grade 3-4 thrombocytopenia in 81% of the patients. Grade 3-4 neutropenia was observed in 50% of the patients. Moderate to severe infections were seen in 13 patients. Summary These results indicate that the combination of bortezomib, bendamustine and prednisone is effective and well tolerated in patients with relapsed/refractory MM and light chain induced renal failure. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Increased Serum Levels of Uric Acid Are Associated with Sudomotor Dysfunction in Subjects with Type 2 Diabetes Mellitus

2011 ◽  
Vol 2011 ◽  
pp. 1-5 ◽  
Author(s):  
N. Papanas ◽  
M. Demetriou ◽  
N. Katsiki ◽  
K. Papatheodorou ◽  
D. Papazoglou ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Uric Acid ◽  
Colour Change ◽  
Serum Levels ◽  
Group A ◽  
Group B

The aim of this paper was to assess serum uric acid (SUA) levels in patients with type 2 diabetes mellitus (T2DM) with or without sudomotor dysfunction (evaluated by the Neuropad test). We included 36 T2DM patients with sudomotor dysfunction (group A: mean age63.1±2.6years) and 40 age-, gender-, renal function- and T2DM duration-matched patients without sudomotor dysfunction (group B: mean age62.1±3.1years). SUA was significantly higher in group A (P<0.001). There was a significant correlation between SUA and Neuropad time to colour change in both groups (group A:rs=0.819,P<0.001; group B:rs=0.774,P<0.001). There was also a significant positive correlation between SUA and CRP in both groups (group A:rs=0.947,P<0.001; group B:rs=0.848,P<0.001). In conclusion, SUA levels were higher in T2DM patients with sudomotor dysfunction than those without this complication. The potential role of SUA in sudomotor dysfunction merits further study.

scholarly journals Study of High sensitive C - reactive protein and Gamma-glutamyl transferase in Type 2 Diabetes Mellitus with Hypertension

2020 ◽  
Vol 11 (3) ◽  
pp. 3478-3483
Author(s):  
Ramya S ◽  
Sureka Varalakshmi V ◽  
Uma Maheswari K ◽  
Chandan Bala R
Keyword(s):  
Diabetes Mellitus ◽  
Gamma Glutamyl Transferase ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Significant Difference ◽  
Group A ◽  
Hs Crp ◽  
Group B ◽  
Glutamyl Transferase

C-reactive protein (CRP), produced by the hepatocytes is a primary inflammatory marker of T2DM. Higher levels of gamma-glutamyl transferase enzyme (GGT) and Hs CRP (High sensitive CRP)are associated with the complication of poor glycemic control.This study was aimed to find the association of Hs CRP and GGT for cardiovascular risk factors in Type 2 diabetes mellitus (T2DM)and Hypertension in the suburbs of Chennai. This study includes 57 subjects with T2DM and Hypertension (Group A) and 62 subjects with T2DM (GroupB) within the age group of 40-60 years. FBS, HbA1C, Hs CRP, GGT and blood pressure were determined. Statistical analysis was performed using Statistical Package for the SPSS 17 version. Mean values of FBS, blood HbA1C, Hs CRP and GGT were significantly higher among participants of Group A than Group B. Significant difference of FBS, HbA1C were found between the two groups. In contrast, no significant difference of GGT was found between the groups. Differences were considered statistically significant at two-sided P < 0.05. Within the group, Hs CRP shows the significance and positive correlation with FBS, SBP and DBP. Still, GGT does not show any significance in Group A. In contrast, in Group B, both Hs CRP and GGT shows the importance and positive correlation with FBS and HbA1C.It is concluded that high levels of HsCRP are associated with T2DM and Hypertension, indicating increased cardiovascular risk, and it should be included in regular monitoring of type-2 diabetic patients.

scholarly journals Clinical appraisal of Lodhradi Kashaya on type 2 diabetes mellitus patients

2017 ◽  
Vol 4 (1) ◽  
pp. 58
Author(s):  
Varun K. Singh ◽  
K. R. C. Reddy
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Blood Glucose ◽  
Dosage Form ◽  
Dose Group ◽  
Group A ◽  
Group B

<p class="abstract"><strong>Background:</strong> <span lang="EN-IN">Lodhradi Kashaya (LKSD) is basically ayurvedic kwath dosage form, described as Madhumehajeet (winner of diabetes mellitus) in ayurvedic classics Basavarajeeyam and the same formulation in Vaidya Chintamani and Charaka Samhita too. The aim of this study was to assess prospectively the drug’s ability in management of type 2 diabetes. </span></p><p class="abstract"><strong>Methods:</strong> <span lang="EN-IN">Total 31 patients were taken following the guideline mention in CCRAS protocol for diabetes mellitus research. They are divided into two groups, group A and B, given LKSD 4 g &amp; 2 g TDS respectively for three-month follow up. They are investigated against their blood glucose, HbA1C and liver profile tests. Patients were also investigated for subjective parameters viz polyurea, polyphagia, exhaustion and constipation and their response has also been noted regarding palatability acceptance and ease of administration.</span></p><p class="abstract"><strong>Results:</strong> <span lang="EN-IN">Patients has responded positively for formulation. Decrease in FBS and PPBS were found highly significant (P ˂ 0.001) in both groups but more in higher dose (group A). Decrease in HbA1C is also found highly significant in both groups. In LFT, SGOT level were also decreased more in group B in comparison to group A, and it is significant (P = 0.017 and 0.002). SGPT level were also decreased more in group B in comparison to group A, and it is significant in group B (P= 0.085 and 0.002).  </span></p><p class="abstract"><strong>Conclusions:</strong> LKSD is having astringent taste due to tannins and phenols in it. It was found significant not only in controlling blood sugar but also in management of other factors related to diabetes mellitus.</p>

scholarly journals Once daily versus twice daily Linagliptin effect on glycemic levels in type 2 diabetes mellitus- an observational study

2017 ◽  
Vol 5 (10) ◽  
pp. 4403
Author(s):  
Riyaz Mohammed ◽  
Mohammed Azfar Ali
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Observational Study ◽  
Plasma Concentrations ◽  
Fixed Dose ◽  
Once Daily ◽  
Group A ◽  
Group B

Background: DPP-4 is widely distributed in endothelial cells, pancreas, uterus, liver, salivary glands, lymph node, spleen, and thymus. DPP-4 regulates glucagon-like peptide (GLP)-1, and glucose-dependent insulin tropic peptide (GIP) which leads to glucose homeostasis via enhancing insulin secretion and suppression of glucagon, which results in control of post-prandial and fasting hyperglycemia.Methods: These 40 patients who were enrolled as per the inclusion criteria of receiving metformin dosage of 2 gram per day in established type 2 diabetes mellitus patients with no comorbidities. these patients were divided randomly into two groups comprising of 20 patients each, group A received linagliptin 5 mg per day in addition to metformin 1gm twice daily whereas group B received linagliptin 5 mg per day in a fixed dose (Linagliptin + metformin) of 2.5/1000 twice daily.Results: In the present observational study, the mean age in group A was 46.7±9.4 compared to 51.65±9.9 in group B, p >0.05, mean BMI in group A was 27.8±1.1 compared to 27.28±0.93 in group B p >0.05, Mean FBS in group A was 157.9±24.1 compared to 146.2±21.8 in group B p >0.05, Mean PPBS in group A was 245.8±32.7 compared to 246.2±39.3 in group B p >0.05 and Mean HbA1c in group A was 7.67±0.58 compared to 7.6±0.5 in group B p >0.05. Group A patients were initiated on once daily linagliptin, there was a significant reduction in FBS, PPBS and HbA1c at the end of 6 months p <0.001. Similarly, Group B patients who were initiated on twice daily linagliptin also showed a significant reduction in FBS, PPBS and HbA1c at the end of 6 months p <0.001.Conclusions: The addition of linagliptin to metformin treatment was effective and well tolerated in patients with type 2 diabetes. Linagliptin add-on to metformin during the early course of treatment helps in delaying the exhaustion of pancreatic islet function. Plasma concentrations of linagliptin decline in at least a biphasic manner with a long terminal half-life (>100 hours), related to the saturable binding of linagliptin to DPP-4. The prolonged elimination phase does not contribute to the accumulation of the drug. Addition of linagliptin to metformin has shown a significant reduction in FBS, PPBS and HbA1c.

Efficacy and Safety of Empagliflozin as Add-On Therapy in Patients of Type-2 Diabetes Mellitus

2022 ◽  
Vol 9 (1) ◽  
pp. 24-27
Author(s):  
Nauman Wazir ◽  
Shafqat Ur Rehman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Side Effects ◽  
Glycaemic Control ◽  
Group A ◽  
Group B ◽  
Tract Infections ◽  
Mycotic Infections

OBJECTIVES: To assess efficacy of two doses i.e., 10 mg and 25 mg in lowering the glycated haemoglobin (HbA1C) and fasting blood glucose (FBG) in patients of type 2 diabetes mellitus (T2DM) having suboptimal glycaemic control on maximal doses of Metformin and Sitagliptin, and to see the frequency of its side-effects. METHODOLOGY: The study design was a randomized control trial. Fifty nine adult patients of T2DM who were already on 2000 mg of Metformin and 100 mg of Sitagliptin and were having suboptimal glycaemic control (HBA1C >7% and <12%) were randomized to two groups, one group receiving 10 mg (Group A) and the other group receiving 25 mg of empagliflozin (Group B) as an additional treatment. HbA1C and FBG were taken before and 12 weeks after addition of empagliflozin in both the groups. Side effects of empagliflozin such as urinary tract infections (UTI) and genital mycotic infections were also recorded in both the groups. RESULTS: Total patients in-group A were 31 and their mean age was 51.48±4.29 years. In-group B there were 28 patients and their mean age was 52.39±5.20 years. There was a statistically significant reduction of both HbA1C and FBG in both the groups after empagliflozin treatment; (p=0.000) for both HbA1C and FBG in both the groups. Although numerically UTI and genital mycotic infections were more than pre-treatment numbers, they were not statistically significant (p>0.05). CONCLUSION: Empagliflozin can be safely added to the oral anti-diabetic regimen of patients with type 2 diabetes mellitus who have suboptimal glycaemic control and results in significant improvement in HbA1C.

scholarly journals Efficacy of green jackfruit flour as a medical nutrition therapy replacing rice or wheat in patients with type 2 diabetes mellitus: a randomized, double-blind, placebo-controlled study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
A. Gopal Rao ◽  
K. Sunil Naik ◽  
A. G. Unnikrishnan ◽  
James Joseph
Keyword(s):  
Diabetes Mellitus ◽  
Nutrition Therapy ◽  
Controlled Study ◽  
Medical Nutrition Therapy ◽  
Double Blind ◽  
Double Blind Placebo ◽  
Group A ◽  
Group B ◽  
Medical Nutrition

Abstract Background/Objectives Medical nutrition therapy along with pharmacological interventions as a multidisciplinary approach is required to treat type 2 diabetes mellitus (T2DM). This study evaluated the efficacy of Jackfruit365™ green jackfruit flour as an integral part of daily meal in patients with T2DM. Subjects/Methods This was a randomized, double-blind, placebo-controlled study conducted between May 2019 and February 2020. Patients of either sex aged ≥18 to ≤60 years with a diagnosis of T2DM for >1 year receiving oral antihyperglycemic agents were randomized (1:1) to receive either jackfruit flour 30 g/day (Group A) or placebo flour (Group B) (breakfast and dinner) daily for 12 weeks replacing an equal volume of rice or wheat flour. The primary endpoint was a mean change in glycosylated hemoglobin (HbA1c). Other endpoints were mean changes in fasting plasma glucose (FPG), postprandial plasma glucose (PPG), lipid profile, and body weight. The independent t-test was used to compare changes between the groups. Results A total of 40 patients were enrolled (n = 20 each). A significantly higher reduction in HbA1c was observed in Group A compared to Group B from baseline to week 12 [−2.73 mmol/mol (−0.25%) vs. 0.22 mmol/mol (0.02%), p = 0.006]. The mean change in FPG and PPG was significantly higher in Group A than that of Group B (p = 0.043 and p = 0.001). The continuous glucose monitoring showed decreasing mean blood glucose in 7 days of administration of jackfruit flour meal. Conclusion Patients from Group A had a significantly higher reduction in HbA1c, FPG, and PPG than Group B demonstrating the efficacy of jackfruit flour in glycemic control as medical nutrition therapy replacing an equal volume of rice or wheat flour in daily meal. Clinical trial registry CTRI/2019/05/019417.

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