Comparative study: Efficacy and tolerability of vildagliptin vs. pioglitazone as an add-on therapy to metformin in poorly controlled type 2 diabetes mellitus patients in Punjab

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P)Original Research Article ISSN: 2394-0034 (O)Comparative study: Efficacy and tolerabilityof vildagliptin vs. pioglitazone as an add-ontherapy to metformin in poorly controlledtype 2 diabetes mellitus patients in Punjab Amita Jindal1*, Rupinder Kaur2, Mahesh Jindal31Senior Lecturer, Department of Pharmacology, Maharaja Ganga Singh Dental College and Research Centre, Sriganganagar, Rajasthan, India2Lecturer, Department of Pharmacology, Guru Nanak Dev Dental College and Research Institute, Sunam, Punjab, India3Opthalmologist, Jagdamba Charitable Eye Hospital, Sriganganagar, Rajasthan, India *Corresponding author email: [email protected] to cite this article: Amita Jindal, Rupinder Kaur, Mahesh Jindal. Comparative study: Efficacy andtolerability of vildagliptin vs. pioglitazone as an add-on therapy to metformin in poorly controlledtype 2 diabetes mellitus patients in Punjab. IAIM, 2015; 2(1): 83-94. Available online at www.iaimjournal.comReceived on: 13-12-2014 Accepted on: 06-01-2015AbstractIntroduction: The incidence of diabetes in urban Punjab is on the rise and the number of diabetics isincreasing year by year.Material and methods: This 24 week study was designed to compare vildagliptin versus pioglitazoneas an add-on therapy in patients of type 2 diabetes mellitus inadequately controlled with metforminalone in Punjabi population. Sixty patients were randomized in two groups to receive eithervildagliptin 100 mg (group 1) or pioglitazone 30 mg (group 2) in addition to metformin 1000 mg. Theprimary efficacy end point was change in FBG, PPG and HbA1c. Secondary end point included lipidprofile, body weight and peripheral edema.Results: There was no significant difference between mean reduction in FBG, PPG and HbA1c in bothgroups. There was significant decrease in mean body weight in group 1 in contrast to significantincrease in group 2. Both the treatment groups reported a significant decrease in TG, TC, LDL andincrease in HDL.Conclusion: Vildagliptin displays robust efficacy with the added benefits of a much lower risk ofperipheral edema, hypoglycemia and no weight gain, making it a promising alternative topioglitazone as an add-on therapy to metformin in Punjabi population.International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 83Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P)Key words ISSN: 2394-0034 (O)Diabetes mellitus, Vildagliptin, Pioglitazone. (dipeptidyl peptidase-4 inhibitors) and which increase insulin sensitivity (thiazoloidinediones)Introduction become available and can provide an attractive alternative for use in combination withType 2 diabetes mellitus (T2DM) is a global metformin [7].epidemic with an estimated worldwide Pioglitazone is an insulin sensitizer or aprevalence of 6% (246 million people) in 2007 thiazolidinedione which acts by improvingand forecast to rise to 7.3% (380 million) by insulin sensitivity at the cellular level. It reduces2025 (IDF, 2006). The prevalence of diabetes is insulin resistance by binding to PPAR γ whichsteadily increasing in the developing countries results in change of expression of genes involvedlike India [1]. India had 40.9 million diabetics in in regulating glucose and lipid metabolism,2006 and it is expected to increase to 69.9 insulin signal transduction and other tissuemillion by 2025 [2]. The incidence of diabetes in differentiation.urban Punjab is on the rise and the number ofdiabetics is increasing year by year [3]. Vildagliptin is a potent and selective dipeptidyl peptidase-4 (DPP-4) inhibitor that prevents theIn addition to diet and exercise, the majority of rapid degradation of endogenous glucagon-likepeople with diabetes need drug therapy to peptide-1 (GLP-1) and glucose-dependentachieve optimal blood glucose levels. insulinotropic peptide (GIP) and increasesMonotherapy with oral antidiabetic agents is the plasma levels of their intact, active form. Byfirst line pharmacologic treatment option. stabilizing endogenous incretin hormones atHowever, patients with more severe diabetes physiological concentrations, DPP-4 inhibitorsare managed with dual therapy [4, 5]. increase the sensitivity to glucose of both insulinMetformin is the most commonly prescribed and glucagon secretion (i.e., increase insulinfirst line antidiabetic drug worldwide, but due to secretion and suppress glucagon secretion in athe progressive worsening of blood glucose glucose-dependent manner), thereby loweringcontrol during the natural history of type 2 glucose levels. DPP-4 inhibitors are thus the firstdiabetes, combination therapy usually becomes oral agents addressing the dual α- and β- isletnecessary [6]. cells dysfunction present in T2DM [8, 9, 10, 11].Adding a sulfonylurea to metformin has been The potential effects of various antidiabetic drugthe conventional and the gold standard classes on weight balance are well recognized.combination therapy for decades. However, this Both insulin and insulin secretagoguescombination substantially increases the risk of (sulfonylureas and glinides) promote weighthypoglycemia resulting in symptoms or gain, especially in regimens designed to achieveincreased food intake to avoid or treat them. intensive glycemic control. ThiazolidinedionesTherefore, the need for alternative combination (TZDs) are associated with weight gain, whiletherapies was warranted. metformin is generally associated with weight neutrality or weight loss. Incretin-basedRecently, newer agents which induce a glucose- therapies, including glucagon-like peptide (GLP)-dependent stimulation of insulin secretion 1 receptor agonists and dipeptidyl peptidaseInternational Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 84Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)(DPP)-4 inhibitors, are associated with weight period, with chronic intestinal disease, withloss or weight neutrality [5]. history of hypersensitivity to the test drug, pregnant and lactating women were excludedPresent study examined the efficacy and from the study.tolerability, with a special focus on the weightneutrality of the DPP-4 inhibitor vildagliptin as Intervention drugscompared to TZDs pioglitazone (vildaglitin plus After meeting the inclusion criteria, patientsmetformin versus pioglitazone plus metformin) were randomized into two groups of 30 each onin the diabetic patients inadequately controlled the basis of additional anti hyperglycemic drugswith metformin alone. As Punjabi population on to be given. To group 1, Tab. Vlidagliptin 50 mghigh risk of weight gain during their diabetes BD orally was given for 24 weeks and to group 2,medication, a rational drug combination (dual or Tab. Pioglitazone 15 mg BD orally for 24 weekstriple therapy) is required to achieve better was given and the patients were directly startedefficacy and tolerability. at this dose. To check compliance and ensure regular medication by the patient, a log bookMaterial and methods was checked regularly which was given to each patient.Study design and settings On the start of the study, (Day 0), after takingThis was multi centered, open, randomized the history of the patients and doing the clinicalparallel study evaluating the comparative effect examination, routine investigations were sent.of vildagliptin and pioglitazone in combination The baseline FBG, PPBG, HbA1C and lipid profilewith metformin (1000 mg BD) on glycaemic and were obtained after 12 hour overnight fasting.lipid profile in diabetic patients over a period of Initially patients were followed after 15 days and24 weeks in punjab. Written informed consent subsequently every month up to 24 weeks. FBGwas obtained from all the patients prior to their and PPBG were recorded at interval of 4 weeksenrollment. Flow of the participants through the while HbA1C and lipid profile were recorded atstudy including randomization, medications and 12 weeks intervals.drop outs were as per Chart - 1.Inclusion criteria Statistical analysisPreviously diagnosed type 2 diabetes mellitus The results were tabulated as mean ± standard(DM) patients in the age group of 30-70 years of deviation (SD) and analyzed using student’s teither sex, on metformin (1000 mg BD) for a test. The level of significance was determined asminimum of ≥ 4 weeks and whose FBG >126 its ‘p’ value with p> 0.05 taken as not significant,mg/dl, PPBG >200 mg/dl and HbA1C between 7- p < 0.05 taken as significant at 5% significance9%. level, p < 0.01 taken as significant at 1% significance level and p < 0.001 taken as highlyExclusion criteria significant.Patients with history of Type 1 DM, those whohad experience acute metabolic diabetic Resultscomplications in past 6 months, with renalfailure, liver failure, cardiac failure, who are Demographics and baseline characteristicslikely to undergo surgery during the study Sixty patients (33 females and 27 males) who were randomized (by random number tables)International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 85Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)and completed the study were included in the statistically significant difference between the 2analysis. In both the groups, maximum number groups was observed.of patients was in the age group of 50-60 yearsand least number of patients was within 30-40 Fasting HDL level during 24-week treatment wasyears of age. Mean age in group 1 was 56 ± 3 as per Chart - 5. A statistically significantyears and in group 2 was 57 ± 4 years. There was increase of serum HDL was observed after 12no statistically significant difference in age and 24 weeks (P < 0.001) compared withdistribution between the two groups. baseline in both groups but no statistically significant difference was noticed between the 2Baseline mean Body mass index (BMI) of groups.patients in group 1 was 28.1±1.4 kg/m2 and ingroup 2 was 28.6±1.2 kg/m2 indicating that Tolerabilitymajority of the patients in both the groups were During the 24-week study, all the treatmentsin the overweight range and there was no appeared to be well tolerated. Vildagliptinstatistically significant difference in BMI added to metformin was generally wellbetween the two groups at the start of study as tolerated, the frequency of any specific adverseper Table – 1. effect was generally low and most adverse events were considered to be mild andEfficacy unrelated to study medication. Adverse eventsTime course of the mean FPG and PPBG during like weight gain, headache and peripheral24-week treatment with the vildagliptin and edema were reported in the patients onpioglitazone as add on therapy to metformin pioglitazone and metformin dual therapy.was as per Chart - 2. There was a statisticallysignificant decrease of FPG and PPBG after 4, 8, Body weight did not change from a mean12, 16, 20 and 24 weeks (P < 0.001) compared baseline to endpoint in patients receivingwith baseline in both groups, and we did not vildagliptin, but increased similarly in patientsobserve any significant differences between the receiving pioglitazone. 13 patients (43%) out of2 groups. 30 in pioglitazone group showed a mean weight gain of 1.2± 0.5 kg after 24 weeks of therapyTime course of the mean HbA1c during 24-week whereas no weight gain was observed intreatment was as per Chart - 3. The adjusted patients receiving vildagliptin therapy.mean reduction in HbA1c from baseline toendpoint was statistically significant after 12 and Peripheral edema was reported in 3 patients24 weeks (P <0.001) in both groups, without any (10%) out of 30 in pioglitazone group but theresignificant differences between the 2 groups. was no such case reported in vildagliptin group.Changes in fasting lipid parameters observed Hypoglycemia was limited to one mild event induring 24-week treatment with vildagliptin and patient receiving vildagliptin and pioglitazone aspioglitazone as add on therapy to metformin an add-on therapy to metformin. No severewas as per Chart – 4 and Chart - 5. There was a hypoglycemic events were reported in both thestatistically significant decrease of serum TC, TG groups.and LDL after 12 and 24 weeks (P < 0.001)compared with baseline in both groups, and no No major changes or consistent trends over time were observed for any hematological,International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 86Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)biochemical, urinalysis parameter or vital signs, Bolli (24 week study) on 576 T2DM patientsand the frequency of treatment-emergent ECG reported simillar significant reduction in HbA1cabnormalities was low and comparable in all (p ≤ 0.001), with both vildagliptin andtreatment groups. pioglitazone as add on to metformin [15].Discussion In a 58 week study conducted by Derosa and 26 month study conducted by Saufert on T2DMThe present work represents the first report on patients with combination of pioglitazone andthe effects of a vildagliptin added to metformin metformin FBG reduced by 21 mg/dl and 32versus pioglitazone added to metformin in mg/dl, PPG reduced by 29 mg/dl and 63 mg/dl,Punjab population. The main findings of this HbA1c reduced by 1.4% and 0.9% respectivelystudy were that in patients with T2DM [16, 17].inadequately controlled by metforminmonotherapy, addition of the DPP-4 inhibitor Regarding fasting lipid parameters bothvildagliptin produced statistically significant and vildagliptin and pioglitazone had a similar impactclinically meaningful reductions in HbA1c level; on each of the parameters, with an increase inthe combination had a good overall tolerability HDL and decrease in TC, TG and LDL levels.profile and was associated with a very low However the extent to which lipid parametersincidence of hypoglycemia. affected favorably with pioglitazone was greater than that with vildagliptin.In our study there was significant reduction in Various studies reported significant reduction inFBG, PPG and HbA1c levels of T2DM patients on TC, TG and LDL with pioglitazone [18, 19, 20] andvildagliptin and pioglitazone as add on therapy increase in HDL [18]. Various studies has shownto metformin. These findings were similarly similar effect of viladagliptin on lipid profile [11,reported in various studies. 14, 21].In a 40 week study conducted by Ahren on 279 DPP-4 inhibitors are body weight-neutral asT2DM patients significant HbA1c (p ≤ 0.001), shown in many studies. This body weightFBG (p ≤ 0.0057) and PPG (p ≤ 0.0001) reduction neutrality is different from the increase in bodywas found with combination of vildagliptin and weight which is associated with treatment withmetformin [8]. Similarly 24 week study thiazolidinediones, sulphonylureas and insulinconducted by Bosi on 544 T2DM patients [12, 15, 22, 23, 24, 25, 26, 27].significant HbA1c (p ≤ 0.001), FBG (p ≤ 0.003)reduction was found with combination of Various authors in their study reportedvildagliptin and metformin [12]. increased in body weight with pioglitazone add on to metformin [15, 17, 28, 29] whereas there24 week study conducted by Goodman and 52 is no significant change in the body weight withweek study conducted by Ferrannini on T2DM vildagliptin add on therapy with metformin [8,patients on combination therapy of vildagliptin 14, 26, 30, 31, 32].and metformin , there was significant reductionin HbA1c (p ≤ 0.001), in both study [13, 14]. The incidence of peripheral edema was found in 5.9% [33], 9.3% [34], of the patient with pioglitazone and metformin combinationInternational Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 87Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)whereas there is no such case of peripheral weight neutrality, contrasting favorably with theedema was reported with vildagliptine as add on weight gain generally observed withtherapy to metformin [25, 30, 32]. sulfonylureas and thiazolidinediones (TZDs) are the key points, which make the DPP-4 inhibitorsIn summary, the multi centered, open, stand out. Therefore, it is no surprise that thisrandomized parallel study evaluating pharmacological class is expected to play ancombination therapy with vildagliptin and increasing role in the management of T2DM.metformin showed statistically significant andclinically meaningful reductions in HbA1c when Vildagliptin and pioglitazone when added tovildagliptin was added to metformin, that were metformin treatment are effective in improvingevident across all demographic and disease glycemic control for 24 weeks in patients withsubgroups. In patients with T2DM inadequately type 2 diabetes. In this study, the efficacy andcontrolled with metformin, the addition of tolerability of vildagliptin was comparable tovildagliptin (100 mg daily) was equally effective pioglitazone on the main parameters HbA1c,as that of pioglitazone (30 mg daily). Efficacy FPG, PPG, lipid profile, and adverse events likewas well preserved over 24 weeks. Fasting and peripheral edema and weight gain.post prandial plasma glucose were significantlyreduced; and the beneficial effects on glucose The combination of vildagliptin and metformin,control was clearly accompanied by consistent two oral anti-diabetic agents withimprovements of parameters for β-cell function. complementary mechanisms of action, providesThe effects on fasting lipids were neutral and, in superior efficacy and allows more patients tocontrast to the pioglitazone/metformin reach their glycemic targets compared tocombination there was weight gain. Overall the continuing metformin monotherapy, withouttolerability profile was good, with in particular increasing the risk of hypoglycemia, withoutno risk of hypoglycemia, peripheral edema and exposing to weight gain and without alteringweight gain with vildagliptin and metformin common cardiovascular risk factorscombination therapy. (hypertension and lipid profile).Conclusion Vildagliptin displays robust efficacy with the added benefits of a much lower risk ofT2DM is often accompanied by other conditions hypoglycemia and no weight gain, making it a(i.e. overweight/obesity with associated promising alternative to pioglitazone as add-onmetabolic syndrome, high residual CV risk), therapy to metformin in Punjab population.which are considered as risk factors andthereby, could further affect both morbidity and Referencesmortality. DPP-4 inhibitors provide effective andconsistent glycemic control. Compared to other 1. King H, Aubert RE, Herman WH. Globaloral hypoglycemic agents, DPP-4 inhibitors burden of diabetes, 1995-2025:produce similar reductions in blood glucose Prevalence, numerical estimates andglycated hemoglobin (HbA1c) levels, but they projections. Diabetes Care, 1998; 21:offer several attractive clinical advantages. A 1414-1431.negligible risk of hypoglycemia, especially muchlower than that observed with sulfonylureas, 2. Mohan V, Sandeep S, Deepa R, Shah B, Varghese C. Epidemiology of type 2International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 88Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P)diabetes: Indian scenario. Indian J Med ISSN: 2394-0034 (O) 9. Balas B, Baig MR, Watson C, et al. TheRes, 2007; 125: 217-230. dipeptidyl peptidase iv inhibitor3. Zafar J, Bhatti F, Akhtar N, Rasheed U, vildagliptin suppresses endogenousHumayun S, Waheed A, et al. Prevalence glucose production and enhances isletand risk factors for diabetes mellitus in a function after single-dose administrationselected urban population of a city in in type 2 diabetic patients. J ClinPunjab. J Pak Med Assoc, 2011; 61: 40- Endocrinol Metab, 2007; 92: 1249–1255.47. 10. Mari A, Sallas WM, He YL, et al.4. Rodbard HW, Jellinger PS, Davidson JA, Vildagliptin, a dipeptidyl peptidase-ivet al. Statement byan American inhibitor, improves model-assessedAssociation of Clinical beta-cell function in patients with type 2Endocrinologists/American College of diabetes. J Clin Endocrinol Metab, 2005;Endocrinology consensus panel on type 90: 4888–4894.2 diabetes mellitus: an algorithm for 11. Rosenstock J, Foley JE, Rendell M, et al.glycemic control. Endocr Pract., 2009; Effects of the dipeptidyl peptidase-iv15: 540–559. inhibitor vildagliptin on incretin5. Nathan DM, Buse JB, Davidson MB, et al. hormones, islet function, andMedical management of hyperglycemia postprandial glycemia in subjects within type 2 diabetes: A consensus impaired glucose tolerance. Diabetesalgorithm for the initiation and Care, 2008; 31: 30–35.adjustment of therapy: A consensus 12. Bosi E., Camisasca RP, Collober C,statement of the American Diabetes Rochotte E, Garber A J. Effects ofAssociation and the European vildagliptin on glucose control over 24Association for the Study of Diabetes. weeks in patients with type 2 diabetesDiabetes Care, 2009; 32: 193–203. inadequately controlled with metformin.6. Turner RC, Cull CA, Frighi V, Holman RR. Diabetes Care, 2007; 30: 890−895.Glycemic control with diet, sulfonylurea, 13. Goodman M, Thurston H, Penman J.metformin, or insulin in patients with Efficacy and tolerability of vildagliptin intype 2 diabetes mellitus: Progressive patients with type 2 diabetesrequirement for multiple therapies inadequately controlled with metformin(UKPDS49). JAMA, 2005; 281: 1999. monotherapy. Horm Metab Res, 2009;7. David M, Kendall MD, Robert M. 41: 368−373.Cuddihy MD, Richard M. Bergenstal MD. 14. Ferrannini E, Fonseca V, Zinman B,Clinical Application of Incretin-Based Matthews D, Ahren B, Byiers S, et al.Therapy: Therapeutic Potential, Patient Fifty-two-week efficacy and safety ofSelection and Clinical Use. The Ame J vildagliptin vs. glimepiride in patientsMed., 2009; 122 (6A): 37-50. with type 2 diabetes mellitus8. Ahren B, Gomis R, Standl E, Mills D, inadequately controlled on metforminSchweizer A. Twelve- and 52-week monotherapy. Diabetes Obes Metab,efficacy of the dipeptidyl peptidase IV 2009; 11: 157−166.inhibitor LAF237 in metformin-treated 15. Bolli G, Dotta F, Colin L, Minic B,patients with type 2 diabetes. Diabetes Goodman M. Comparison of vildagliptinCare, 2004; 27: 2874−2880. and pioglitazone in patients with type 2 diabetes inadequately controlled withInternational Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 89Copy right © 2015, IAIM, All Rights Reserved.

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Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P)term therapy with addition of ISSN: 2394-0034 (O) controlled, multiple-dose study. Hormpioglitazone to metformin compared Metab Res, 2007; 39: 218−223.with the addition of gliclazide to 33. Einhorn D, Rendell M, Rosenzweig J,metformin in patients with type 2 Egan JW, Mathisen AL, Schneider RL.diabetes: a randomized, comparative Pioglitazone hydrochloride instudy. Diabetes Metab Res Rev, 2005; combination with metformin in the21: 167–174. treatment of type 2 diabetes mellitus: A30. Kikuchi M, Abe N, Kato M, Terao S, randomized, placebo-controlled study.Mimori N, Tachibana H. Vildagliptin The Pioglitazone 027 Study Group. Clindose-dependently improves glycemic Ther, 2000; 22: 1395–1409.control in Japanese patients with type 2 34. Rosenstock J, Brazg R, Andryuk PJ, Lu K,diabetes mellitus. Diabetes Res Clin Stein P. Efficacy and safety of thePract, 2009; 83: 233−240. dipeptidyl peptidase-4 inhibitor31. Scherbaum WA, Schweizer A, Mari A, sitagliptin added to ongoing pioglitazoneNilsson P M, Lalanne G, Jauffret S, et al. therapy in patients with type 2 diabetes:Efficacy and tolerability of vildagliptin in A 24-week, multicenter, randomized,drug-naive patients with type 2 diabetes double-blind, placebo-controlled,and mild hyperglycaemia. Diabetes Obes parallel-group study. Clin Ther, 2006; 28:Metab, 2008; 10: 675−682. 1556−1568.32. Dejager S, Razac S, Foley JE, SchweizerA. Vildagliptin in drug-naïve patientswith type 2 diabetes: A 24-week,double-blind, randomized, placeboSource of support: Nil Conflict of interest: None declared.Table - 1: Demographics and baseline characteristics of the study groups.Demographic Vildagliptin + metformin Pioglitazone + metformin (Group 1) (Group 2)No. of patientsSex ratio (male/female) 30 30Age (years), mean±SD 14/16 13/17Body weight (kg), mean±SD 56.50±3.06 57.43±4.21BMI (kg/m2 ), mean±SD 80.4±0.2 80.1±0.3 28.1±1.4 28.6±1.2International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 91Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P)Chart – 1: Flow of study. ISSN: 2394-0034 (O) 79 patients were screened for eligibilityEnrolment 12 patients were excluded Randomized (n=67) • 9 patients were not meeting inclusion criteria • 3 patients declined to participate 35 patients were allocated in Allocation 32 patients were allocated in group 1 group 2 (Vildagliptin 50 mg BD + metformin 1000 mg BD) (Pioglitazone 15 mg BD + metformin 1000 mg BD)4 patients didn’t come back forfollow up and 1 patient had Follow up 2 patients didn’t come back for followshifted to insulin therapy due to Analysis uppersistent rise in HbA1c Analyzed (n=30) Analyzed (n=30)International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 92Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)Chart - 2: FBG and PPBG levels during treatment with vildagliptin + metformin (group 1) andpioglitazone + metformin (group 2) over a period of 24 weeks.Blood glucose (mg/dl) 220 GROUP 1 FBG 210 GROUP 1 PPBG 200 GROUP 2 FBG 190 GROUP 2 PPBG 180 170 4 8 12 16 20 24 160 Duration (weeks) 150 140 130 120 110 0Chart - 3: Glycosylated hemoglobin levels (HbA1c) during treatment with vildagliptin + metformin(group 1) and pioglitazone + metformin (group 2) over a period of 24 weeks.HbA1c (%) 10 GROUP 1 HbA1c GROUP 2 HbA1c 9 8 7 6 5 0 4 8 12 16 20 24 Duration (weeks)International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 93Copy right © 2015, IAIM, All Rights Reserved.

Efficacy and tolerability of vildagliptin vs. Pioglitazone ISSN: 2394-0026 (P) ISSN: 2394-0034 (O)Chart - 4: Serum total cholesterol (TC) and TG levels during treatment with vildagliptin + metformin(group 1) and pioglitazone + metformin (group 2) over a period of 24 weeks. TC & TG level (mg/dl) 200 GROUP 1 TC 190 GROUP 1 TG 180 GROUP 2 TC 170 GROUP 2 TG 160 150 4 8 12 16 20 24 Duration (weeks) 0Chart - 5: Serum LDL and HDL levels during treatment with vildagliptin + metformin (group 1) andpioglitazone + metformin (group 2) over a period of 24 weeks.HDL &LDL level (mg/dl) 140 GROUP 1 HDL 120 GROUP 1 LDL 100 GROUP 2 HDL GROUP 2 LDL 80 40 35 4 8 12 16 20 24 0 Durati on (weeks)International Archives of Integrated Medicine, Vol. 2, Issue 1, January, 2015. Page 94Copy right © 2015, IAIM, All Rights Reserved.