Combination Therapy Of Vildagliptin Research Articles

Evaluating the Efficacy, Safety, and Tolerability of Combination Therapy of Dapagliflozin and Linagliptin Over Dapagliflozin and Vildagliptin in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin.

Background Type 2 diabetes mellitus (T2DM) patients commonly undergometformin monotherapy.This study aims to compare the efficacy, safety, and tolerability of combination therapy of dapagliflozin plus linagliptin versus dapagliflozin plus vildagliptin as add-on therapy in T2DM patients inadequately controlled on metformin. Methodology This was an 18-week, multicenter, randomized, double-blind, active-controlled, parallel-group, phase III clinical study. About 236 participants were randomly assigned to receive either a fixed-dose combination of dapagliflozin 10 mg plus linagliptin 5 mg tablets or a fixed-dose combination of dapagliflozin 10 mg plus vildagliptin SR 100 mg tablets added to metformin monotherapy. The primary outcome was the mean change in hemoglobin A1c (HbA1c) from baseline to the end of week 16. The key secondary endpoints were mean change in postprandial blood glucose (PPBG), fasting blood glucose (FBG), body weight, and the proportion of participants achieving HbA1c less than 7.0%. Results The dapagliflozin/linagliptin combination therapy showed a more significant change in HbA1c from baseline to the end of 16 weeks (mean reduction: -1.59% vs. -1.25%) compared to dapagliflozin/vildagliptin (p < 0.0001). Additionally, compared to the dapagliflozin/vildagliptin group, the dapagliflozin/linagliptin group demonstrated a significant reduction in both PPBG (mean reduction: -59.99 mg/dL vs. -55.34 mg/dL) and FPG (mean reduction: -32.91 mg/dL vs. -26.78 mg/dL). A total of 18 adverse events were reported in 17 (7.20%) participants, all of which were mild and resolved completely. There were no serious adverse events. Conclusions Compared to dapagliflozin and vildagliptin combination therapy, dapagliflozin and linagliptin fixed-dose combination provided clinically significant improvements in glycemic control. Because of its effectiveness, safety, and tolerability, the fixed-dose combination of dapagliflozin and linagliptin was a better option for treating T2DM patients who had previously only received metformin monotherapy.

Ефективність і патогенетичне обґрунтування застосування вілдагліптину у хворих на цукровий діабет 2-го типу

Актуальність. Інгібітори дипептидилпептидази 4-го типу (ДПП-4), маючи інкретинову активність, впливають на основні патогенетичні механізми цукрового діабету (ЦД) 2-го типу. Вілдагліптин є інноваційним препаратом класу інгібіторів ДПП-4 з унікальними характеристиками фармакокінетики, ефективність і безпека якого вивчалися в плацебо-контрольованих дослідженнях. Мета дослідження: вивчення фармакотерапевтичної ефективності, безпеки й переносимості препарату Гліптар виробництва ПАТ «Київмедпрепарат» (Україна) у терапії хворих на ЦД 2-го типу. Матеріали та методи. У дослідження було включено 49 пацієнтів із ЦД 2-го типу. До включення в дослідження хворі отримували монотерапію метформіном у дозі не менше за 1000 мг на добу принаймні упродовж останніх шести місяців. Тривалість перебігу ЦД 2-го типу в середньому становила 6,2 ± 1,8 року. Пацієнти сформували дві групи для подальшого спостереження. 29 пацієнтам, які до цього часу отримували препарати метформіну в дозі до 2000 мг/добу, був додатково призначений препарат Гліптар (вілдагліптин) у дозі 50 мг двічі на добу. Пацієнти другої групи (n = 20) продовжували прийом метформіну двічі на день в дозі 2000 мг/добу. Результати. Через 12 тижнів у хворих першої групи на тлі терапії метформіном у поєднанні з вілдагліптином рівень НbА1с вірогідно знизився до 6,42 ± 0,21 %, глікемія натще — до 6,14 ± 0,22 ммоль/л, глікемія постпрандіальна — до 8,63 ± 0,23 ммоль/л. На тлі комбінованого лікування у хворих на ЦД 2-го типу відзначалися зниження маси тіла на 1,18 кг, а також тенденція до зниження індексу маси тіла з 31,49 ± 1,08 кг/м2 до 29,98 ± 0,76 кг/м2. Рівень імунореактивного інсуліну становив після лікування в першій групі 14,08 ± 1,83 мкОд/мл (при початковому 21,11 ± 2,03 мкОд/мл), індекс HOMA-IR — 3,14 ± 0,21 (проти початкового 6,28 ± 1,42). Вірогідне зниження показників вуглеводного обміну, інсулінорезистентності можна оцінювати як позитивну динаміку завдяки комбінованому лікуванню. Висновки. З огляду на отримані переваги подвійної терапії в лікуванні хворих на ЦД 2-го типу відповідно до загальноприйнятої покрокової терапії на другому етапі пацієнтам, які отримують метформін і не досягли цільового глікемічного контролю, доцільно призначати препарат вілдагліптину. Комбінована терапія вілдагліптином у поєднанні з метформіном забезпечує комплексну дію на чинники ризику серцево-судинних захворювань у вигляді запобігання розвитку гіперінсулінемії та зниження інсулінорезистентності.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management.

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged >18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients showed a loss of weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p<0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin as monotherapy and combination therapy of vildagliptin and metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well tolerated in Indian patients with T2DM continuum.

Data on vildagliptin and vildagliptin plus metformin combination in type-2 diabetes mellitus management

It is of interest to evaluate the clinical effectiveness and safety of vildagliptin as monotherapy and combination therapy of vildagliptin and metformin for the management of type 2 diabetes mellitus (T2DM) patients in Indian settings. The study included patients with T2DM (aged &gt;18 years) receiving vildagliptin monotherapy and vildagliptin in combination with metformin therapy of various strengths. Data related to demographics, risk factors, medical history, glycated hemoglobin (HbA1c) levels, and medical therapies were retrieved from medical records. Out of 9678 patients (median age, 52.0 years), 59.1% were men. A combination of vildagliptin and metformin (50/500 mg) was the most commonly used therapy (54.8%), and the median duration of therapy was 24.0 months. The predominant reason for selecting vildagliptin therapy was to improve HbA1c levels (87.8%). A total of 87.5% of patients required dosage up-titration. Vildagliptin therapy was used in patients with T2DM and associated complications (peripheral neuropathy, CAD, nephropathy, retinopathy, autonomous neuropathy, stroke/TIA, and peripheral artery disease). Among 5175 patients who experienced body weight changes, a majority of patients had lost weight (68.6%). The target glycemic control was achieved in 95.3% of patients. The mean HbA1c levels were significantly decreased post-treatment (mean change: 1.34%; p&lt;0.001). Adverse events were reported in 0.4% of patients. Physicians rated the majority of patients as good to excellent on the global evaluation of efficacy and tolerability scale (98.9%, each). Vildagliptin with or without metformin was an effective therapy in reducing HbA1c helps in achieving target glycemic control, and was well-tolerated in Indian patients with T2DM continuum.

94-LB: Long-Term Clinical Benefits of Early Combination Approach in Latin American Subpopulation of VERIFY Study

The VERIFY study showed long-term clinical benefits of the early combination therapy of vildagliptin with metformin (EC) vs. traditional stepwise approach initiating with metformin monotherapy (MET) in a multinational population of newly diagnosed adult patients with T2D (HbA1c 6.5-7.5%). This sub-analysis evaluated the outcomes in Latin American population. The primary endpoint was time to initial treatment failure (TF), defined as HbA1c ≥7.0% at two consecutive scheduled visits after randomization. The time to second TF was tested when patients in both groups were receiving and failing on the combination. A total of 537 eligible patients, 58.8% females, were randomly assigned to either receive the EC (n=266) or MET (n=271). EC significantly reduced the relative risk (RR) of time to initial TF by 47% vs. MET (HR [95% CI] 0.53 [0.4, 0.7]; p&amp;lt;0.0001). A total of 66.3% vs. 46.4% of patients achieved the primary endpoint in the MET and EC groups, with a median (interquartile range: IQR) time to TF of 33.4 (12.2, 60.1) and 59.8 (27.5, not estimable) months, respectively. The RR for time to secondary TF was reduced by 31% with EC (p&amp;lt;0.0092). With EC, HbA1c levels were consistently lower and higher proportion of patients maintained HbA1c &amp;lt;7.0%. Both treatment approaches were well tolerated, and only 3.2% participants discontinued the study due to adverse events. Seven patients in EC vs. three in MET, reported mostly one mild hypoglycemic episode, none leading to discontinuation. Similar to the global population, the long-term clinical benefits were achieved more frequently and without tolerability issues with the strategy of EC vs. standard-of-care MET in this Latin American population. Disclosure S. Vencio: None. J. Manosalva: None. C. Mathieu: Advisory Panel; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Intrexon, MannKind Corporation, Medtronic, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk Inc., Pfizer Inc., Roche Diagnostic USA, Sanofi. Research Support; Self; Intrexon, Novo Nordisk Inc., Sanofi. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk Inc., Sanofi. P. Proot: None. P.M. Paldanius: Other Relationship; Self; Novartis AG. Funding Novartis AG

Glycaemic durability of an early combination therapy with vildagliptin and metformin versus sequential metformin monotherapy in newly diagnosed type 2 diabetes (VERIFY): a 5-year, multicentre, randomised, double-blind trial

Early treatment intensification leading to sustained good glycaemic control is essential to delay diabetic complications. Although initial combination therapy has been suggested to offer more opportunities than a traditional stepwise approach, its validity remains to be determined. Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes (VERIFY) was a randomised, double-blind, parallel-group study of newly diagnosed patients with type 2 diabetes conducted in 254 centres across 34 countries. The study consisted of a 2-week screening visit, a 3-week metformin-alone run-in period, and a 5-year treatment period, which was further split into study periods 1, 2, and 3. Patients aged 18-70 years were included if they had type 2 diabetes diagnosed within 2 years prior to enrolment, and centrally confirmed glycated haemoglobin A1c (HbA1c) of 48-58 mmol/mol (6·5-7·5%) and a body-mass index of 22-40 kg/m2. Patients were randomly assigned in a 1:1 ratio either to the early combination treatment group or to the initial metformin monotherapy group, with the help of an interactive response technology system and simple randomisation without stratification. Patients, investigators, clinical staff performing the assessments, and data analysts were masked to treatment allocation. In study period 1, patients received either the early combination treatment with metformin (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and vildagliptin 50 mg twice daily, or standard-of-care initial metformin monotherapy (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and placebo twice daily. If the initial treatment did not maintain HbA1c below 53 mmol/mol (7·0%), confirmed at two consecutive scheduled visits which were 13 weeks apart, patients in the metformin monotherapy group received vildagliptin 50 mg twice daily in place of the placebo and entered study period 2, during which all patients received the combination therapy. The primary efficacy endpoint was the time from randomisation to initial treatment failure, defined as HbA1c measurement of at least 53 mmol/mol (7·0%) at two consecutive scheduled visits, 13 weeks apart from randomisation through period 1. The full analysis set included patients who received at least one randomised study medication and had at least one post-randomisation efficacy parameter assessed. The safety analysis set included all patients who received at least one dose of randomised study medication. This study is registered with ClinicalTrials.gov, NCT01528254. Trial enrolment began on March 30, 2012, and was completed on April 10, 2014. Of the 4524 participants screened, 2001 eligible participants were randomly assigned to either the early combination treatment group (n=998) or the initial metformin monotherapy group (n=1003). A total of 1598 (79·9%) patients completed the 5-year study: 811 (81·3%) in the early combination therapy group and 787 (78·5%) in the monotherapy group. The incidence of initial treatment failure during period 1 was 429 (43·6%) patients in the combination treatment group and 614 (62·1%) patients in the monotherapy group. The median observed time to treatment failure in the monotherapy group was 36·1 (IQR 15·3-not reached [NR]) months, while the median time to treatment failure time for those receiving early combination therapy could only be estimated to be beyond the study duration at 61·9 (29·9-NR) months. A significant reduction in the relative risk for time to initial treatment failure was observed in the early combination treatment group compared with the monotherapy group over the 5-year study duration (hazard ratio 0·51 [95% CI 0·45-0·58]; p<0·0001). Both treatment approaches were safe and well tolerated, with no unexpected or new safety findings, and no deaths related to study treatment. Early intervention with a combination therapy of vildagliptin plus metformin provides greater and durable long-term benefits compared with the current standard-of-care initial metformin monotherapy for patients with newly diagnosed type 2 diabetes. Novartis.

The effects of vildagliptin compared with metformin on vascular endothelial function and metabolic parameters: a randomized, controlled trial (Sapporo Athero-Incretin Study 3)

BackgroundDipeptidyl peptidase-4 (DPP-4) inhibitors may have protective effects in the early stage of atherosclerosis in patients with type 2 diabetes, although similar effects in advanced atherosclerosis were not shown in recent randomized placebo-controlled studies. Therefore, we investigated the efficacy of DPP-4 inhibitor on endothelial function and glycemic metabolism compared with high-dose metformin.MethodsIn this multicenter, open-labeled, prospective, randomized, parallel-group comparison study, patients with type 2 diabetes treated with low-dose metformin (500–750 mg/day) were enrolled and randomly assigned to a vildagliptin, a DPP-4 inhibitor, add-on group (Vilda) or a double dose of metformin group (high Met) for 12 weeks. Flow-mediated dilation (FMD) and serum metabolic markers were assessed before and after treatment. In addition, glycemic control and metabolic parameters were also assessed.ResultsNinety-seven subjects (aged 58.7 ± 11.0 years; body mass index, 25.9 ± 4.4 kg/m2; HbA1c, 7.3 ± 0.5%; FMD, 5.8 ± 2.6%) were enrolled. Eight subjects dropped out by the end of the study. There were no significant differences between the two groups in baseline characteristics. After 12 weeks, HbA1c was significantly improved in the Vilda group compared with the high Met group (− 0.80 ± 0.38% vs. − 0.40 ± 0.47%, respectively; p < 0.01). However, there were no significant differences in FMD (− 0.51 [− 1.08–0.06]% vs. − 0.58 [− 1.20–0.04]%). Although the apolipoprotein B/apolipoprotein A1 ratio was significantly reduced in the Vilda group compared with baseline (0.66–0.62; p < 0.01), the change did not differ significantly between the two groups (− 0.04 vs. 0.00; p = 0.27). Adiponectin levels were significantly increased in the Vilda group compared with the high Met group (0.75 μg/mL vs. 0.01 μg/mL; p < 0.01).ConclusionsRegardless of glycemic improvement, combination therapy of vildagliptin and metformin did not affect endothelial function but may exert favorable effects on adipokine levels and lipid profile in patients with type 2 diabetes without advanced atherosclerosis.

INFLUENCE OF VILDAGLIPTIN AND GLIQUIDONE COMBINATION ON P-GLYCOPROTEIN FUNCTIONAL ACTIVITY AND EXPRESSION ON THE BACKGROUND OF NORM AND IN EXPERIMENTAL ALLOXAN-INDUCED DIABETES MELLITUS TYPE 2

In the in vivo study on rabbits investigated the effect of the vildagliptin and gliqui-done combination on the background of norm and experimental alloxan-induced diabetes mellitus (DM) type 2 on the P-glycoprotein (P-gp, ABCB1 protein) functional activity and its expression in the tissues of the jejunum, liver, kidney and the blood-brain barrier. Introduction of combination of vildagliptin at a dose of 5 mg/kg and gliquidone 10 mg/kg body weight on the background of norm for 14 days did not result in P-glycoprotein changes. On the 5-day of the cancellation of this combination observed inhibition of transporter protein functional activity without altering its expression. In the combination therapy of vildagliptin and gliquidone alloxan-induced diabetes type 2 showed complete recovery of P-glycoprotein functional activity and expression reduced on the pathology background. On the 5-day of treatment withdrawal again occurred inhibition of functional activity of the transporter protein and a decrease in its expression.

Pattern of Onset and Risk Factors for Peripheral Oedema During Vildagliptin Use: Analysis from the Vildagliptin Prescription-Event Monitoring Study in England.

Clinical trials have identified peripheral oedema (PO) as an adverse event of vildagliptin (an oral anti-diabetic drug [OAD]). A post-marketing study (PMS) was conducted to advance the understanding of vildagliptin use and particular safety concerns identified within the risk-management plan. PMS objectives included comparing the hazards between vildagliptin monotherapy and combination therapy for selected a priori identified risks, including PO. This study was a per-protocol supplementary analysis to investigate the pattern of onset and effect of vildagliptin combination therapy on PO risk. The PMS used an observational cohort design. OAD exposure, selected risk factors and outcome data were collected from general practitioners in England regarding vildagliptin users for the 6-month period after starting treatment. Data analysis comprised univariate case/non-case analysis, time-to-onset analysis and Cox proportional hazard models to estimate hazard ratios (HR) of PO adjusting for selected patients' baseline characteristics. The study cohort included 4828 patients (median age 63years; interquartile range [IQR] 54-71), 2692 of whom were male (55.8%). The crude cumulative hazard of PO was 19.09 cases (95% confidence interval [CI] 13.54-26.10) per 1000 person-years; 50% of cases occurred during the first 34days of treatment. A significantly faster time to PO onset was observed in patients prescribed concomitant sulfonylureas versus other treatment combinations (log rank test [LRT] p=0.0365); in patients with a prior history of PO (LRT p<0.001), arrhythmia (LRT p=0.0003) or hypertension (LRT p=0.0125); and in patients aged ≥60years (LRT p=0.0047). Similarly, the case/non-case univariate analysis indicated that patients with PO were older; had a higher prevalence of a history of either arrhythmia, hypertension or PO; and frequently used a sulfonylurea in combination. In the hazard function analysis, only sex and prior PO history had a profound effect on risk of PO after starting vildagliptin. Furthermore, effect modification was observed between sex and prior PO history; in male patients of average age (62years), the HR was 12.84 (95% CI 4.96-33.23); in females, it was 1.44 (95% CI 0.32-6.40). In this planned supplementary analysis, the findings suggest that PO occurred most frequently within 1month after starting treatment with vildagliptin, and previous PO history and male sex in elderly patients were important predictors of this risk. The observation that concomitant use of a sulfonylurea may also increase PO risk early after starting treatment should be taken into consideration if prescribing OADs in combination with vildagliptin.

Stromal Derived Factor 1 alpha (SDF-1a) in a Dual Therapy with the DPP-4 Inhibitor 1 Vildagliptin does not Enhance Beta Cell Function but Improves Glucose Clearance after Oral Glucose in Streptozotocin Diabetic Mice

Pancreatic alpha cells secrete glucagon-like peptide 1 (GLP-1), the production of which is enhanced by the chemokine stromal derived factor 1 (SDF-1). Since SDF-1, like GLP-1, is a substrate of dipeptidyl peptidase-4 (DPP-4), we examined whether dual therapy with SDF-1 and a DPP-4 inhibitor would preserve beta cell function and mass in diabetes. Diabetes was induced by daily injections of streptozotocin for 5 days. One diabetic group was treated with daily injections of SDF-1 alpha or vehicle for 5 days. These mice were concurrently treated with either the DPP-4 inhibitor vildagliptin or vehicle and they remained on vildagliptin or vehicle for an additional 3 weeks. Glucose clearance and beta cell function was evaluated from glucose and insulin data during OGTTs performed after 0, 2 and 4 weeks of treatment. Beta cell mass was determined histologically. Body weight did not differ between diabetic groups during the study. OGTT data showed that diabetic mice treated with SDF-1 alpha in combination with vildagliptin had increased glucose clearance which was not observed with vildagliptin alone. In contrast, vildagliptin alone enhanced beta cell function with no further enhancement by the combination with SDF-1 alpha. Beta cell mass and islet GLP-1 content were not altered by the treatments. In conclusion, SDF-1 alpha and vildagliptin combination therapy improves glucose clearance in streptozotocin induced diabetes in the mouse by an effect which seems independent from enhanced beta cell function.

Efficacy and safety of nateglinide plus vildagliptin combination therapy compared with switching to vildagliptin in type 2 diabetes patients inadequately controlled with nateglinide.

To investigate the efficacy and safety of vildagliptin, a potent dipeptidyl peptidase-4 inhibitor, as add-on to nateglinide, compared with switching to vildagliptin in Japanese type2 diabetes patients poorly controlled with nateglinide. A total of 40 patients inadequately controlled with nateglinide were randomized to the switching group (n=20, switching from nateglinide to vildagliptin) or combination group (n=20, nateglinide plus vildagliptin). A meal tolerance test was carried out at weeks 0 and 24. The mean changes in glycated hemoglobin from baseline to week 24 were -1.2±0.3% and -0.3±0.5% in patients of the combination and switching groups, respectively, and the difference between the groups was statistically significant (P<0.001). The mean changes in area under the curve of glucose from 0 to 180min (AUC0-180min) from baseline to week 24 was -361±271.3mmol·min/L in patients of the combination group compared with 141±241.9mmol·min/L in those of the switching group (P<0.001). The incidence of hypoglycemic events was low (three in the combination group), and none of the patients developed severe hypoglycemia. Although the addition of vildagliptin to nateglinide did not significantly increase insulin secretion relative to glucose elevation (ISG) after meal load (ISG0-180min: AUC0-180min insulin/AUC0-180min glucose) in comparison with that in baseline, the mean ISG0-30min 24weeks after addition of vildagliptin to nateglinide was significantly higher than that at baseline. In contrast, switching from nateglinide to vildagliptin reduced the mean ISG0-180min, relative to baseline. The combination therapy of vildagliptin and nateglinide is effective and safe in Japanese type2 diabetes, and the improved glycemic control is as a result of augmentation of nateglinide-induced early phase insulin secretion. This trial was registered with UMIN (no. ID000004010).

Beneficial effects of vildagliptin combined with miglitol on glucose tolerance and islet morphology in diet-controlled db/db mice

Dipeptidyl peptidase-4 (DPP-4) inhibitors improve glycemic control in patients with type 2 diabetes primarily by increasing plasma active glucagon-like peptide-1 (GLP-1) levels. While various combination therapies based on DPP-4 inhibitors have been proposed for treatment of type 2 diabetes, the effects of combination therapy of DPP-4 inhibitors and alpha-glucosidase inhibitors on β-cell function are less characterized. We evaluated the effects of long-term treatment with vildagliptin, a DPP-4 inhibitor, on metabolic parameters and β-cell function, in combination with miglitol, an alpha-glucosidase inhibitor, in diet-controlled db/db mice. In this study, 6-week-old male db/db mice were provided with standard chow twice a day for 6weeks. Meal tolerance tests and glucose tolerance tests showed that the combination therapy of vildagliptin with miglitol, but not each alone, suppressed postprandial glycemic excursion, enhanced postprandial active GLP-1 levels and prevented deterioration of glucose tolerance in the db/db mice. The combination treatment did not alter β-cell mass, but resulted in preserved expression of glucose transporter 2, Zinc transporter 8 and MafA and reduced the number of α cells. These results suggest that the combination of vildagliptin and miglitol prevents the development of overt diabetes in diet-controlled pre-diabetic db/db mice by normalizing postprandial glucose and incretin response, and by preserving β-cell structure and the expression of factors essential for β-cell function.