Prevalence and Association of Risk Factors According to Liver Steatosis and Fibrosis Stages among Nonalcoholic Fatty Liver Disease Patients with Type 2 Diabetes Mellitus in India: A Cross-sectional Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD) are linked to the global diabetes epidemic, leading to increased disease progression and adverse health outcomes. The renaming of NAFLD to metabolic dysfunction-associated steatotic liver disease (MASLD) at the 2023 European Association for the Study of the Liver Congress highlights the complex relationship between metabolic disorders and liver health. Taking this into consideration, we aimed this study to identify prevalence and risk factors associated with the stages of NAFLD in individuals with T2DM in the Indian population. MATERIALS AND METHODS: This observational, cross-sectional study was conducted on 1,521 T2DM patients at Dr Panikar's Speciality Care Centre, Mumbai, between September 1, 2022 and October 31, 2022. Demographic parameters such as age, gender, height, weight, and anthropometric parameters such as body mass index (BMI) and waist circumference were measured. Liver fibrosis and steatosis stages were identified by vibration-controlled transient elastography (VCTE) using FibroScan®. RESULTS: The prevalence of liver steatosis was 75.1% among the 1,521 diabetes cases [S0 (24.9%), S1 (15.1%), S2 (24%), and S3 (36%)], whereas the prevalence of liver fibrosis was 28.0% [F0 (72%), F1 (19%), F2 (5%), F3 (1.5%), and F4 (3.4%)]. The S1 (p = 0.012), S3 (p = 0.001), F1 (p = 0.001), and F2 (p = 0.001) grades showed significant gender-related changes, demonstrating a positive connection. Furthermore, waist circumference was associated with disease severity in both liver steatosis and fibrosis stages (p = 0.001), but BMI was solely associated with the degree of steatosis (p = 0.001). The mean age differences between these categories, however, did not reach statistical significance (p-values of 0.149 and 0.078, respectively, for the steatosis and fibrosis grades). CONCLUSION: The study reveals a high prevalence of NAFLD (steatosis and fibrosis) in T2DM patients, increasing the risk of advanced fibrosis. In T2DM patients with risk factors including waist circumference and BMI, appropriate screening and intervention are required.

Evolution of Metabolic Syndrome in Newly Diagnosed Type 2 Diabetes Mellitus Asian-Indian Patients Over the Last 15 Years using Adult Treatment Panel III of the National Cholesterol Education Program, World Health Organization, and International Diabetes Federation Criterion.

AIM: A retrospective observational study was undertaken to assess the changing trends in the incidence of metabolic syndrome (MetS) in Asian-Indian patients with newly diagnosed type 2 diabetes (T2D) using Adult Treatment Panel III of the National Cholesterol Education Program (NCEP-ATP III), World Health Organization (WHO), and the International Diabetes Federation (IDF) criteria. The overall and gender-wise pattern of MetS and its components were also evaluated. MATERIALS AND METHODS: Newly diagnosed T2D patients (n = 10,950)visiting Dr Panikar's Diabetes Care Centre from 2004 to 2019 with retrievable electronic medical records were selected. The incidence of MetS in these patients was studied using NCEP-ATP III, WHO, and IDF criteria in three separate timelines, namely, group I (2004-2008), group II (2009-2013), and group III (2014-2019). Overall and gender-wise, the incidence of various components of the MetS was also studied and compared across the three groups. All data were analyzed by using the Statistical Software Statistical Package for the Social Sciences (SPSS) version 10.0. Continuous variables were summarized by the number of observations (mean, standard deviation or median with minimum and maximum) and categorical values (calculating frequencies with percentages). Chi-square was used to estimate the incidence of MetS using different criteria and gender-wise patterns of the MetS components for the three periods. Other variables, such as mean body mass index (BMI), were assessed by applying variance analysis (ANOVA test). All values were reported based on a two-sided ANOVA test, and all the statistical tests were interpreted at a 5% level of significance. RESULTS: In the current study, the overall incidence of MetS observed among the study population was 80.9, 65.4, and 69.8% using NCEP-ATP III, WHO, and IDF criteria, respectively. The incidence of MetS across the three timelines (i.e., from 2004 to 2019) with all the diagnostic criteria showed a steady increase. An analysis of the individual components of MetS revealed a high incidence of central obesity across all subgroups, followed by hypertension and dyslipidemia. Central obesity was prevalent in nearly 85.9% of patients in 2014-2019 vs 78.6% in the 2004-2008 subgroup. Similarly, the incidence of hypertension and overall dyslipidemia [i.e., high triglycerides (TGs) and low high-density lipoprotein-cholesterol (HDL-C)] was 77.8% and 68.2% in the former vs 67.9% and 59.6% in the latter, respectively. The incidence of all three MetS components, along with fasting sugar, showed a statistically significant and progressive increase over the years, with prevalence in group III (2014-2019) being the highest. Women were found to be more centrally obese and more dyslipidemic compared to men, whereas men were found to be more hypertensive. CONCLUSION: The study shows a high incidence of MetS in Asian-Indian patients with newly diagnosed T2D. The incidence of MetS was significantly higher with the NCEP-ATP III diagnostic criteria than with WHO and IDF criteria. A steady rise in the incidence of MetS was observed over the study period of 2004-2019. Among the components of MetS, the incidence of central obesity, elevated TG levels, and low HDL-C were found to be higher in the female population than in males, whereas the incidence of hypertension was higher in males. Stringent lifestyle measures, along with appropriate pharmacological management, might help mitigate the risks associated with MetS.

Study of the Efficacy of Uptitrating Teneligliptin Dose from Standard Dose (20 mg) to High Dose (40 mg) in Patients with Type II Diabetes Mellitus.

AIM: To study the efficacy of uptitrating the dose of Teneligliptin from 20 to 40 mg in patients with type II diabetes mellitus. METHOD: A retrospective, comparative analysis was undertaken in 853 type II diabetes mellitus patients (499 males and 354 females) who had follow-up records for more than 6 months. These patients were uncontrolled after use of atleast three oral antidiabetic drugs (OADs) and Teneligliptin 20 mg was added as the fourth drug. Patients who remained uncontrolled with the addition of 20 mg of Teneligliptin at the end of 3 months and were switched to receive 40 mg of Teneligliptin daily were included in this study. Results were analyzed at 3 and 6 months to ascertain efficacy of high-dose (40 mg) Teneligliptin. All other OADs remained the same in both groups. In all patients, the fasting blood glucose, postprandial blood glucose, and hemoglobin A1c (HbA1C) were evaluated and compared. RESULT: A total of 853 patients whose dose of Teneligliptin was increased from 20 to 40 mg were included in the study. At the end of 3 months after using Teneligliptin 40 mg, mean reduction in HbA1C was 0.5% (p-value 0.154). Similarly, mean reduction in fasting blood sugar (FBS) and postprandial blood sugar (PPBS) was 6.5 and 3.6 mg/dL, respectively (p-value 0.234 and 0.143). At the end of 6 months after using Teneligliptin 40 mg HbA1C showed no change but mean FBS and PPBS showed a modest reduction of 14.6 and 14 mg/dL, respectively (p-value < 0.001). CONCLUSION: The results of our study show that there was no statistically significant improvement in glycemic parameters when dose of Teneligliptin was increased from 20 to 40 mg at 3 months. But at 6 months, the FBS and PPBS showed a modest reduction of 14.6 and 14 mg/dL, respectively (p-value < 0.001) but the HbA1C showed no change.

Prescribing Patterns and Response to Antihyperglycemic Agents Among Novel Clusters of Type 2 Diabetes in Asian Indians.

Aim: To assess the prescribing patterns and response to different classes of antihyperglycemic agents in novel clusters of type 2 diabetes (T2D) described in India. Materials and Methods: We attempted to replicate the earlier described clusters of T2D, in 32,867 individuals with new-onset T2D (within 2 years of diagnosis) registered between October 2013 and December 2020 at 15 diabetes clinics located across India, by means of k-means clustering utilizing 6 clinically relevant variables. Individuals who had follow-up glycated hemoglobin (HbA1c) up to 2 years were included for the drug response analysis (n = 13,247). Results: Among the 32,867 participants included in the study, 20,779 (63.2%) were males. The average age at diagnosis was 45 years and mean HbA1c at baseline was 8.9%. The same four clusters described in India earlier were replicated. Forty percent of the study participants belonged to the mild age-related diabetes cluster, followed by insulin-resistant obese diabetes (27%), severe insulin-deficient diabetes (21%), and combined insulin-resistant and insulin-deficient diabetes (12%) clusters. The most frequently used antihyperglycemic agents were sulfonylureas, metformin, and dipeptidyl peptidase-4 inhibitors apart from insulin. While there were significant differences in HbA1c reduction between drugs across clusters, these were largely driven by differences in the baseline (pretreatment) HbA1c. Conclusions: In this new cohort, we were able to reliably replicate the four subtypes of T2D earlier described in Asian Indians. Prescribing patterns show limited usage of newer antihyperglycemic agents across all clusters. Randomized clinical trials are required to establish differential drug responses between clusters.

Teneligliptin Real-World Effectiveness Assessment in Patients with Type 2 Diabetes Mellitus in India: A Retrospective Analysis (TREAT-INDIA 2).

INTRODUCTION: Teneligliptin is an antidiabetic medication that has been approved for the management of type 2 diabetes mellitus (T2DM) in Japan, South Korea and India. It is one of the most commonly prescribed antihyperglycaemic agents. The aim of this study was to assess the effectiveness of teneligliptin in improving glycemic control amongst Indian patients with T2DM in a real-world setting. METHODS: This was a retrospective observational study in which a predesigned structured proforma was used to collect information from hospital records of 18 medical centres across India. All participating centres were established primary care hospitals with adequate record keeping, a pre-determined condition in the study design. Data were collected during the period of January 2019 to June 2019. Data extracted from patient records, including glycaemic parameters, concomitant drugs, drug dosage and duration, were collated. The effectiveness of teneligliptin was assessed by analyzing the mean change in glycosylated haemoglobin (HbA1c), fasting plasma glucose (FPG) and post-prandial plasma glucose (PPG) at 12 weeks after initiation of teneligliptin. RESULTS: Data from 10,623 patients were available for analysis. The mean age of the enrolled patients was 51.86 ± 11.76 years. At 12 weeks after initiation of teneligliptin as monotherapy or add-on to other medications (combination therapy), the patients showed a signficant decrease from baseline in mean HbA1c, FPG and PPG. Mean HbA1c dropped from 8.66 ± 1.15% at baseline to 7.67 ± 1.28% at 12 weeks (71 ± 12.6 to 60 ± 14 mmol/mol), with a difference of - 0.99% (95% confidence interval [CI] 0.96-1.02) or - 10.8 (95% CI 10.5-11.1) mmol/mol (p < 0.0001). The mean reductions in FPG and PPG were 43.12 mg/dL (2.39 mmol/L) and 87.73 mg/dL (4.87 mmol/L) (both p < 0.0001) respectively. HbA1c (%) reductions with teneligliptin when used as add-on to metformin, add-on to metformin + sulfonylurea combination and add-on to metformin + sulfonylurea + alpha glucosidase inhibitor combination were 0.76% (8.3 mmol/mol), 1.24% (13.6 mmol/mol) and 1.04% (11.4 mmol/mol), respectively. Teneligliptin also significantly reduced HbA1c (1.13% or 12.4 mmol/mol, p < 0.0001) in patients with impaired renal function, without worsening the estimated glomerular filtration rate. Teneligliptin consistently reduced HbA1c across all three age categories tested-by 1% (10.9 mmol/mol) in patients aged < 60 years, by 1.15% (12.6 mmol/mol) in patients aged 60-75 years and by 0.88% (9.6 mmol/mol) in patients aged > 75 years. CONCLUSION: Teneligliptin significantly improved glycaemic parameters in Indian patients with T2DM when prescribed either as monotherapy or as an add-on to one or more other commonly prescribed antihyperglycaemic agents.

Efficacy of DPP4i as the Fourth Drug in the Management of Type2 Diabetes Mellitus in Asian Indians Poorly Controlled by Use of at least 3 Oral Antidiabetic Drugs.

AIM: To evaluate the efficacy of DPP-4 inhibitors (DPP-4i) as the fourth drug in Asian Indian type2 DM patients uncontrolled inspite of using at least 3 oral anti diabetic drugs. METHODS: A retrospective analysis of 7858 T2DM patients, who received a DPP-4i (Sitagliptin, Vildagliptin, Teneligliptin, Linagliptin and Saxagliptin) as the fourth drug to achieve glycemic control was undertaken. Patients with inadequate glycaemic control despite receiving optimum doses of at least any other three OADs were included in this analysis. RESULTS: Patients were subdivided into 5 groups, based on the DPP-4i used for treatment: Sitagliptin (n=4787), Vildagliptin (n=2205), Teneligliptin (n=775), Linagliptin (n=64) and Saxagliptin (n=27). The mean fasting blood glucose (FPG) was 160.9 ± 20.4 mg/dl and mean post prandial glucose (PPG) was 227.8 ± 26.3 mg/dl. The mean baseline HbA1c was 8.2 ± 1.5 %. The mean duration required to control diabetes with all DPP-4i was 8.2 weeks with significantly lesser time with Sitagliptin (6.8 weeks, p<0.001). 81.5% of the total cases responded to treatment with a DPP-4i (P <0.05). At the end of the monitoring period, there was significant reduction in mean FPG by-28.1 ± 16.1 mg/dL(P=0.001), mean PPG by -55.3 ± 17.0 mg/dL(P=0.001), and mean HbA1c by -1.2 ± 0.7 (P= 0.001). There was no significant difference between the groups with respect to reduction in PPG and HbA1c. CONCLUSION: DPP-4 inhibitors are effective in achieving desired glycaemic goals even when used as a fourth drug in patients with inadequate glycaemic control despite receiving an optimum dose of at least 3 OADs.

Autoimmune Hypoglycemia Relapse on Glucocorticoids, Effectively Treated with Azathioprine.

Autoimmune Hypoglycemia, though very rare in India, but can be challenging to manage. Insulin autoimmune syndrome (IAS) should be considered in any patient with hypoglycemia in the setting of unsuppressed insulin levels associated with anti-insulin or anti insulin receptor antibodies. We are reporting the clinical course of one such case of insulin autoimmune syndrome, who was initially treated with glucocorticoids. The patient relapsed and was later on treated effectively with Azathioprine for glucocorticoids failure and toxicity.

Efficacy of SGLT2 Inhibitors as the Fifth Drug in the Management of Type 2 Diabetes Mellitus in Asian Indians not Controlled with at least 4 Oral Antidiabetic Drugs.

AIM: To evaluate the efficacy of SGLT2 inhibitors as an add-on therapy along with stricter lifestyle modification in Asian Indian type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). METHODOLOGY: A retrospective analysis of data of 808 T2DM patients being treated with an SGLT2 inhibitor (Dapagliflozin, Empagliflozin or Canagliflozin) as an add-on drug in patients with inadequate glycemic control despite receiving optimum doses of at least any four OADs(metformin, sulphonylureas, pioglitazone, DPP4 Inhibitors, alpha-Glucosidase Inhibitors) and who preferred not to initiate insulin. RESULTS: The average age of the patients included was 51.63 years (SD ± 9.88). 57.7% were males. Average weight was 81.95±16.08 kg. Mean duration of diabetes was 34.08±39.04 months. The mean baseline fasting plasma glucose was 198.21 ± 38.21 mg/dl and mean post prandial plasma glucose was 264.22 ± 45.22 mg/ dl. The baseline HbA1c was 8.92 ± 1.47 %. Total 87.4 % of the cases responded to addition of SGLT2 inhibitors during a mean follow-up period of 6 months. The fasting plasma glucose (FBS) was reduced by -63.65 ± 19.93 mg/dl to a mean FBS of 134.57 ± 33.65 mg/dl (P=0.001). The post prandial plasma glucose (PPBS) was reduced by -79.28 ± 23.57 mg/dl to a mean PPBS of 184.94 ± 38.34 mg/dl (P=0.001). The mean HbA1c reduced significantly by -1.63 ± 0.99 % (P= 0.001). The mean weight reduction at 6 months of therapy was -3.03± 01.84 kg that is 3.8 % decrease from baseline (p=0.001).The response in age group < 55 years was 90.9 %, whereas in ≥55 years, it was 82.2% (p=0.001). The males responded more (91.0%) compared to females (82.5%) (p=0.001). Those with BMI < 23.5 kg/ m2 had marginally higher but insignificant response of 93.0% as compared to 87.1% in patients with high a BMI (≥23.5 kg/m2) (p=0.253). Patients with < 5years duration of diabetes responded better (91.8%) as compared to patients with a ≥ 5 years of diabetes (85.4%). CONCLUSION: SGLT2 inhibitors are effective in achieving desired glycemic goals even when used as a fifth add-on drug along with strict lifestyle modification in patients with inadequate glycemic control despite receiving an optimum dose of at least 4 oral antidiabetic drugs (OADs). SGLT2 inhibitors can be effectively used at any stage of diabetes.

Effect of Low (7.5 mg/day), Standard (15 mg/ day) and High (30 mg/day) Dose Pioglitazone Therapy on Glycemic Control and Weight Gain in Recently-Diagnosed Type 2 Diabetes Patients.

Objective: To study the effect of different daily doses of pioglitazone on glycemic control and weight gain in newly-diagnosed type 2 diabetes mellitus (DM) patients. Research Design and Methods: Chart reviews were performed of recently-diagnosed (<24 months) type 2 DM patients receiving oral therapy including pioglitazone. Patients were excluded if they had heart disease, liver dysfunction or renal insufficiency; or were being treated with insulin or the incretin drugs. Patients had received 7.5 mg/day (Group A), 15 mg/day (Group B) or 30 mg/day (Group C) of pioglitazone. Characteristics including demographics, weight, body mass index and glycated hemoglobin (HbA1c) were recorded at baseline and at six months. Results: At the end of six months, there was significant weight gain in all groups from baseline (P<0.01). Weight gain was greatest in Group C (2.72 kg; SD=2.97), intermediate in Group B (1.62 kg; SD=2.91) and least in Group A (0.88 kg; SD=2.77). The difference was statistically significant between Groups A and C; and Groups B and C; but not between Groups A and B. There was no difference between HbA1c lowering in the three groups (P>0.05). Dose correlated with weight gain (r=0.254; P<0.001) but not with HbA1c reduction (r=0.012; P=0.85). There was no correlation between HbA1c reduction and BMI increase (r = -0.024; P=0.72). Conclusions: The glycemic effect of pioglitazone is preserved even at lower doses, while the propensity to cause weight gain increases with dose. We suggest that low-dose pioglitazone (7.5 mg/day) should be the preferred dose at which to initiate therapy in recently-diagnosed patients. Pioglitazone is an extremely useful agent in the treatment of type 2 diabetes mellitus (DM) through its actions on alleviating insulin resistance.

Inter-generation comparison of type-2 diabetes in 73 Indian families.

AIMS AND OBJECTIVE: To study type 2 diabetics in 2 generations in the same family and to see if there are any significant differences in their presentations. The study also focused on the non-diabetic siblings to see if there were any differences between them. MATERIAL AND METHODS: Criteria for inclusion: 1. Proband case should have a parent who is a diabetic, 2. Proband case should have at least one sibling who is not diabetic. Entire families of such cases fulfilling the above criteria were included in the study. A detailed questionnaire was filled. This was followed by an examination of all anthropometric measurements like height, weight, waist circumference, hip circumference and blood pressure. Venous blood samples for glucose measurement (fasting and post prandial), HbA1c, renal profile, lipid profile and insulin levels were collected. Urine sample was collected in appropriate containers for microalbuminuria, albumin/creatinine ratio. RESULTS: The study included 73 families, with a total of 307 members (159 male and 148 female). 92 were from 1st generation and 215 from 2nd generation. Of these 182 were diabetics, 81 from 1st generation and 151 from 2nd generation (95 males and 87 females). 125 were non diabetics, 9 from 1st generation and 116 from the 2nd generation (64 males and 61 females). The mean age of onset of diabetes in 1st generation was 55.95 years (SD +/- 9.98) and in 2nd generation was 38.4 years (SD +/- 9.2) (p<0.0001). Body mass index (BMI), waist circumference, Wasist-hip ratio (W/H ratio) and triglycerides, HDL and blood pressure individually did not show any significant differences between the diabetics in both generations. The incidence of metabolic syndrome as per ATPIII criteria was 75.9 % among the 1st generation diabetics. There were only 9 non-diabetics in the first generation and this number was small to derive any statistical significance. Comparison between diabetics and non diabetics in the 2nd generation showed that the incidence of metabolic syndrome as per ATPIII criteria was significantly higher among the diabetics at 62.63% as against 28.45% in the non diabetics. BMI, W/H ratio and lipid profile individually did not show any significant differences between the diabetics and non diabetics. CONCLUSIONS: This study shows that the age of onset of diabetes is much earlier in the present generation being 38.4 years (SD +/- 9.2), as compared to 55.95 years (SD +/- 9.98) in the previous generation. There were no other significant differences between the two generations. In the present generation the incidence of metabolic syndrome as per ATPIII criteria was a significant risk factor for the development of diabetes. 62.63% of the diabetic siblings had metabolic syndrome as compared to 28.45% in the nondiabetic siblings. There were no other significant parameters for early detection of diabetes in this group.

Prevalence of metabolic syndrome in an urban Indian diabetic population using the NCEP ATP III guidelines.

OBJECTIVE: To study the prevalence of metabolic syndrome (MetS) in an urban Indian diabetic population. RESEARCH DESIGN AND METHODS: A total of 5088 type 2 diabetes patients (2908 men and 2180 women) presenting to endocrinology clinics at four centers across Mumbai (a large metropolitan city in India) were selected for the study. Anthropometric (waist circumference), clinical (blood pressure) and biochemical (serum triglycerides, HDL, fasting and post-prandial blood glucose) data were recorded. Patients receiving treatment for hypertension or dyslipidemia were also included in the study and these were considered in the diagnosis of MetS even if the parameters were normal. The National Cholesterol Education Program Adult Treatment Panel III guidelines were used to diagnose MetS. The chi-square test was used to determine statistical significance, which was taken as a p value < 0.05. RESULTS: The prevalence of MetS among urban Indian diabetic patients was 77.2% and was significantly higher in women (87.71%) as compared to men (69.33%) (p < 0.0001). The most prevalent risk factors for MetS were hypertension, followed by hypertriglyceridemia, in men, and central obesity, followed by hypertension, min women. CONCLUSIONS: MetS is highly prevalent in the urban Indian diabetic population. It should be identified by regular screening in individuals from the general population to avert or delay the progression to type 2 diabetes in order to reduce diabetes-related morbidity and mortality.

Induction of long-term glycemic control in type 2 diabetic patients using pioglitazone and metformin combination.

AIMS AND OBJECTIVE: To study the effects of pioglitazone and metformin combination in type 2 diabetics in achieving long-term optimal glycemic control. METHODS AND MATERIALS: Patients whose duration of type 2 diabetes was less than 24 months were selected for the study. 373 such patients meeting the selection criteria were included in the study and were started on triple drug combination therapy. RESULTS: Three hundred seventy three (183 females and 190 males) patients were initiated on a triple drug combination of gliclazide 80 mg, tid, metformin 500 mg tid and pioglitazone 30 mg od. Once controlled, the doses of gliclazide were reduced if the blood glucose levels decreased. Those patients whose plasma glucose remained in the normal range for more than 6 months without the use of a sulphonylurea were considered to be in pharmacological remission. 48 patients were lost to follow up. At the beginning of the study the pre treatment biochemical parameters in these 325 diabetic patients at the time of enrolment were: average FBG of 209.44+/-73.82 mg/dl, PLBG 294.96+/-107.58 mg/dl, and HbA(1c) 11.21+/-3.85. The post treatment glycemic parameters were: FBG was 124.38+/-40.48 mg/dl (p < 0.0001), and PLBG 162.32+/-54.33 mg/dl (p < 0.001), average glycosylated hemoglobin was 6.45+/-2.17 (p < 0.001). After using the triple drug combination pharmacological remission was achieved in 36.3 percent i.e. 118 (60 males and 58 females) patients. The average time required for achieving remission was 4 (+/-3.3) months in males and 5 (+/-4.02) months in females. 118 patients were maintained remission after 2 years of follow up. The average duration of remission is 27 (+/-2.66) months. There was an average weight gain of 2.56 +/- 1.32 kg in both the groups of patients in remission and those who could not achieve remission. CONCLUSIONS: In this study we have found that we could achieve long term glycemic control 'pharmacological remission' in 118 of the 325 patients i.e.36% of type 2 diabetic patients. Insulin sensitizers like pioglitazone along with metformin may induce long-term glycemic control in type 2 diabetic patients.

Beneficial effects of triple drug combination of pioglitazone with glibenclamide and metformin in type 2 diabetes mellitus patients on insulin therapy.

BACKGROUND: The thiazolidinediones are a class of antidiabetes medication that enhance the actions of insulin in muscle, liver, and adipose tissue. Data have been lacking on their use in combination with both sulfonylurea and metformin among patients of type 2 diabetes who are on insulin therapy secondary to failure of routine oral hypoglycemic drugs in controlling their diabetes. OBJECTIVE: To determine the effects of pioglitazone in combination with sulphonylurea and metformin on diabetes control in patients being treated with insulin due to secondary failure of oral hypoglycemic agents. PATIENTS: One hundred and twenty-four consecutive type 2 diabetes patients (mean age, 57.13 years) attending four centres in Mumbai, who were being treated with insulin were selected. They were switched on to triple drug combination of glibenclamide 5 mg, metformin 500 mg and pioglitazone 15 mg along with insulin. Study participants were required to have type 2 diabetes mellitus for atleast 5 years. Patients were excluded if they had any of the following: serum creatinine concentration greater than 1.5 mg/dl, alanine aminotransferase (ALT) level more than two times the upper limit of normal, symptomatic angina, cardiac insufficiency or history of myocardial infarction. RESULTS: Pioglitazone 15 mg with glibenclamide 5 mg and metformin 500 mg, significantly decreased hemoglobin HbA1c level from 11.5% to 7.32% (P < 0.001), average fasting blood glucose from 194.8 mg/ dl to 124.06 mg/dl (p < 0.01), average post-prandial blood glucose from 256.24 to 162.32 mg/dl (p < 0.01). At 6 months, 43.35% of patients did not need to be continued on insulin. The total insulin requirement in 124 patients reduced by 71.81%. There were no significant side effects, liver enzymes were within acceptable levels, average weight gain was 2.23 kg, significant hypoglycemia was observed in 28 patients with two requiring hospitalisation, these patients were those who did not stick to follow-up schedules. CONCLUSIONS: With proper patient selection, pioglitazone with glibenclamide and metformin can be safely used in patients receiving insulin with good results.