Metformin Dual Therapy Research Articles

Cost-effective Analysis of Prescribed Oral Hypoglycemic Agents amongst Pre-obese and Obese Diabetic Patients in a Tertiary Care Hospital in Odisha

Objectives: Diabetes is more prevalent in middle- and higher-income groups and is spreading at an alarming rate. Drug therapy is compulsory because of the chronic and progressive nature of the disease. With such multifactorial background of high prevalence, progressive nature of the disease leading to various complications, increased healthcare cost, and availability of multiple therapeutic regimens prescribed, this study has been done to evaluate the cost-effective analysis of oral hypoglycemic agents. Materials and Methods: This is a prospective, parallel group, and comparative observational study conducted by the Department of Pharmacology in collaboration with the Department of Endocrinology at Kalinga Institute of Medical Sciences, Bhubaneswar. The duration of the study was of 2 years. A total number of 220 patients were selected and based on body mass index, patients were categorized into preobese (new and old diabetic patients) and obese (new and old diabetic patients) categories. In this study, cost-effectiveness analysis (CEA) was done to evaluate the cost differences between two or more medication groups, with a similar clinical effect. Results of CEA are expressed as an average cost-effectiveness ratio or as an incremental cost-effectiveness ratio. Results: From this study, it is observed that in terms of benefit, dual therapy of Metformin and Dapagliflozin was most efficacious followed by Metformin and Sitagliptin as well as Metformin and Glimepiride combinations. If cost is considered, Metformin montherapy and metformin and Glimepiride dual therapy was most cost-effective. In triple regimen, MET+VOG+GLIM combination was seen to be more cost effective than gliptin combination, both in terms of control of FBS as well as PPBS. The cost of treatment goes parallel with duration of disease, being higher in the old cases of long-standing duration. Conclusion: The present study shows that SGLT2 inhibitors are better class of oral hypoglycemics in terms of long-term benefits and this group is prescribed as dual therapy more frequently but cost of therapy is the greatest barrier. Metformin and Sulfonylureas remain the most beneficial combination, both in terms of efficacy and cost. The cost of treatment was varying, depending on the duration of disease, being higher in old cases and lower in new cases.

Evaluation of pharmacokinetic interactions between lobeglitazone, empagliflozin, and metformin in healthy subjects.

ClinicalTrials.gov Identifier: NCT04334213.

Real-world Retrospective Assessment of Initiation and Effectiveness of Dual Combination Therapy with Metformin and Teneligliptin in Drug Naïve Indian Type 2 Diabetes Mellitus Patients (INITIATE)

Introduction: Diabetes Mellitus (DM) has become the leading health concern worldwide over the last few decades. But despite advances in both understanding of the pathophysiology of Type 2 Diabetes Mellitus (T2DM), and the development of new treatment strategies, current management of patients with T2DM remains suboptimal. Initial monotherapy is frequently inadequate in patients with high baseline Glycated Haemoglobin (HbA1c). Thus, initial combination therapy has emerged as an alternative approach. Aim: To assess INItiation and effecTiveness of dual combInation therapy with metformin And Teneligliptin in drug naïvE T2DM patients (INITIATE). Materials and Methods: In this retrospective, multicentre study, newly diagnosed drug naïve T2DM patients failed with diet and exercise prior to screening and initiated with dual therapy of metformin and teneligliptin were enrolled. Data of all the patients prescribed with any therapeutic dose of metformin (250 mg, 500 mg, 750 mg, 1000 mg, 1500 mg, 2000 mg) and teneligliptin (20 mg, 40 mg) was considered. The data was analysed to assess change in glycaemic parameters from baseline to 12 weeks. Paired t-test was applied for statistical results. Results: Data of 7857 patients were analysed. The mean change of Fasting Plasma Glucose (FPG) from baseline {202.29±52.2 mg/dL (11.23±2.89 mmol/L)} to 12 weeks {142.57±34.5 mg/dL (7.91±1.91 mmol/L)} was -59.72±17.7 mg/dL (-3.31±0.98 mmol/L) (p-value <0.0001). The absolute change in mean Postprandial Plasma Glucose (PPG) from baseline {(286.26±80.43 mg/dL (15.89±4.46 mmol/L)} to 12 weeks {(198.30±42.24 mg/dL (11±2.34 mmol/L)} was -87.96±38.19 mg/dL (-4.88±2.12 mmol/L) (p-value <0.0001). Mean HbA1c level was 8.11%±1% (65±10.9 mmol/mol) at baseline and decreased significantly to 7.15%±0.94% (55±10.3 mmol/mol) (p-value <0.0001) with a mean change of -0.96±0.06 (-10.5±0.7 mmol/mol) at 12 weeks. Total 42.83% (n=3365) patients achieved target HbA1c (<7%) at 12 weeks. Conclusion: Initiation of dual therapy with metformin and teneligliptin in drug naïve Indian T2DM patients significantly improved glycaemic control.

Dispensation Patterns of Glucose-Lowering Drugs in Newly Diagnosed Type 2 Diabetes: Routine Data Analysis of Insurance Claims in Germany.

To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

Level of glycemic control among US type 2 diabetes mellitus patients on dual therapy of metformin and sodium–glucose cotransporter 2 inhibitor: a retrospective database study

Objective To assess the level of glycemic control among type 2 diabetes patients on sodium-glucose cotransporter 2 inhibitor (SGLT2i) and metformin dual therapy. Methods Observational, retrospective database study in adult type 2 diabetes mellitus patients from the IQVIA Electronic Medical Record (EMR) database was conducted. The observation period was June 2015 to June 2018. Patient’s earliest encounter in the observation period while on SGLT2i and metformin dual therapy served as the index date. Patients were required to have at least one HbA1c measure in the 12 months prior to the index date and be on SGLT2i and metformin dual therapy and no other antihyperglycemic treatment as of the HbA1c measurement date or any time during the 90 days prior. The associations between sociodemographic factors and clinical burden on achievement of HbA1c <8% were assessed using multivariable logistic regression with backward stepwise selection. Results Of 3491 patients, 2176 (62.3%) achieved HbA1c <8%, with a median distance to goal of 1.1% (IQR 0.5–2.3%) for those not at glycemic target. Mean age was 56.5 years and 52.6% were male. At baseline, 28.3% of patients had established cardiovascular disease/chronic kidney disease, and of those 63.8% had HbA1c <8%. African American patients had lower odds of attaining HbA1c <8% when compared with white patients [OR 0.69], while older patients had marginally higher odds [OR 1.01]. Conclusion Approximately 3 out of 5 patients on metformin and SGLT2i dual therapy achieved HbA1c <8%, with African Americans having a lower likelihood of achieving this glycemic goal.

2208-PUB: Effect of Pioglitazone on HOMA-IR, C-Peptide, HbA1c, and Weight

Aim: To observe the effect of Pioglitazone on improving HOMA-IR, c-peptide status, HbA1c and Weight. Materials and Methods: Inclusion Criteria: Persons with type 2 diabetes since &amp;gt;5 years duration of age 18-50 years, on dual OAD therapy Exclusion Criteria: Other forms of diabetes, pregnant patients or planning for pregnancy. For the study, 116 patients were identified and screened. Baseline investigations and anthropometry was recorded. Pioglitazone was added to the ongoing regimen of single or dual combination therapy for a period of 24 weeks. All patients were called for a total of 6 visits during the study period wherein their glycemic control, hypoglycemia events and medications were reviewed. At the end of 24 weeks, anthropometry, investigations and glycemic control was reviewed. Results: The average c-peptide, HOMA-IR and HbA1c levels had reduced significantly after the addition of Pioglitazone. Those patients who were on dual therapy of metformin with an SGLT2 inhibitor showed no significant weight changes at the end of the study. Other patients who were on monotherapy with metformin, dual therapy with metformin plus other OADs showed weight gain. Conclusion: Pioglitazone is a very effective tool in diabetes management. It shows significant reduction in glycemia. Appropriate combination therapy with SGLT2 inhibitors may curb its issue of weight gain. Disclosure S.V. Sheth: None. M.N. Parekh: None. D. Panchal: None.

SUN-LB112 Efficacy &amp; Safety After Switchover to Remogliflozin in Indian T2DM Patients - a Real World Study

INTRODUCTON: Remogliflozin is new SGLT2i recently approved in India, but more economical than the previously available SGLT2i. It is prudent to evaluate its effectiveness & tolerability in comparison to other SGLT2i in real world setting. METHODS: In this observational retrospective study, medical data from EMR of tertiary care hospital in Kolkata was retrieved. The records of adult Type 2 diabetes mellitus (T2DM) patients who were on a dual therapy of Metformin plus SGLT2i (Canagliflozin, Dapagliflozin or Empagliflozin) for at least 6 months with adequate glycaemic control (HbA1c to target based on age & duration of diabetes) & subsequently switched over to Remogliflozin 100 mg twice daily because of economic reasons were screened. The day of switchover was considered as index day (Day 1) The patient records whose data was unavailable, metformin dose was altered during period of next 6 months, who had evidence of active UTI on index day, were receiving injectable anti-diabetic drugs or had recorded eGFR <45 mL/min were excluded. The effectiveness was assessed in terms of maintenance of HbA1c, FBS, PPBS, body weight after 3 & 6 months of treatment. The safety was assessed by adverse events recorded in medical records in terms of abnormal symptoms, signs or laboratory reported values during the observation period of 6 months & compared to equivalent period of 6 months before index day. The data was collected & analysed using appropriate statistical techniques. RESULTS: After screening, medical records of 50 adult T2DM patients (54% male) were found to be eligible. The mean baseline characteristics on Index day in terms of Age, HbA1c levels, FBS, PPBS, weight & BMI was 51.3±12.5 years, 6.8±0.4%, 108.7±8.1 mg/dL, 144.5±21.3 mg/dL, 65.5±5.7 kg & 25.8±2.8 kg/m2 respectively. After treatment period of 6-months with Remogliflozin-based regimen, the mean HbA1c, FBS, PPBS, -Body weight & BMI was 6.7±0.8%, 110.3±10.5 mg/dL, 138.5±12.7 mg/dL, 66.3±6.5 kg & 25.9±3.2 kg/m2 Mean change from baseline in HbA1c levels, FBS, PPBS, weight & BMI were-0.1±0.19%, -1.6±7.2 mg, -6.0±8.3 mg, +0.8±0.2kg, & +0.1±0.0.7 kg/m2 respectively. These change from baseline of all above parameters were not found to be statistically significant (P>0.05) No events of hypoglycaemia, disturbance in electrolytes or any unusual adverse events were reported. Combined incidence of UTI & genital Mycotic infection was similar during 6 month observation period as compared to 6 months prior to index day. (8% vs 6%) CONCLUSION: In real world clinical practice, replacement of ongoing SGLT2i with Remogliflozin was observed to provide consistent glycaemic control without any tolerability issues. Hence, novel SGLT2i Remogliflozin can be considered as equivalent alternative for SGLT2i based regimen in management of Indian T2DM patients

Factors associated with the discontinuation of dipeptidyl peptidase-4 inhibitors (DPP-4is) after initiation of insulin

Objective: Type 2 diabetes (T2D) is a prevalent health problem. Oral agents, with the exception of metformin, are often discontinued with the initiation of insulin. The objective was to understand the proportion of patients discontinuing dipeptidyl peptidase-4 inhibitors (DPP-4is) and the reasons for the decision to discontinue.Methods: A retrospective study using a health claims database investigated discontinuation of DPP-4i in adult patients on a dual therapy of metformin and DPP-4i who initiated insulin (n = 3391). An online survey administered to 406 physicians in the US examined reasons for discontinuation. Physicians surveyed included endocrinologists (34.5%), general practitioners (32.5%), internal medicine specialists (30.5%), and diabetologists (2.5%), treating a monthly average of 154 patients.Results: Among patients treated with metformin and DPP-4is who were newly prescribed insulin, 33.3 and 57.3% discontinued DPP-4i therapy within 3 and 12 months, respectively. Patients who discontinued DPP-4i therapy had higher out-of-pocket costs and a greater proportion of renal and liver disease. Top 3 responses for discontinuation included adverse events/tolerability issues (58.9%), lack of efficacy/treatment goals not being met (55.4%) and additional cost of DPP-4i with insulin (48.5%). Top 3 responses for continuing DPP-4i included meeting treatment goals (70.7%), using a lower dose of insulin (65.3%) and good tolerability (48.0%). Physician characteristics, such as physician specialty, age, gender and location impacted to some extent the reasons for treatment decisions.Conclusions: A large proportion of patients discontinue DPP-4is in the real world when initiating insulin. The impact of physician characteristics in treatment decisions highlights the need for enhanced physician training and support as new clinical data emerges and therapy options are available.

2431-PUB: Distance from Glycemic Target at the Time of Intensification in Patients with Type 2 Diabetes (T2D) Failing Metformin Dual Therapy in the United States

Several studies have previously reported “clinical inertia” in the sequential treatment of T2D patients. The objective of the study was to quantify the distance from HbA1c target at the time of treatment intensification among patients failing dual therapy of metformin and another oral antihyperglycemic agent (OAHA). This retrospective study was conducted using GE Centricity Electronic Medical Record database (2015 data). Patients included those with diagnosed T2D on metformin dual therapy with at least 12 months of continuous enrollment prior to index date (initiation of dual therapy), documented HbA1c ≥7% and intensifying therapy within two years following index date. Treatment intensification was defined as either addition of another OAHA or initiation of insulin/glucagon-like peptide-1 receptor agonists. Distance from glycemic target was calculated as the median difference of HbA1c from target of 7% at the time of therapy intensification. 864 patients met the study criteria; mean age of 57.5 years, 48% were female, 26.3% had microvascular and 18.4% had macrovascular complications. Median difference from HbA1c target of 7% was 1.4%, with 29% (n=253) of patients between 1 to 2%, and 36% (n=315) greater than 2% distance from HbA1c target. When we excluded those for whom higher HbA1c target may be more appropriate (those ≥65 years, with micro- or macrovascular complications or with history of hypoglycemia), the median difference was 1.6%. This study suggests that majority of metformin dual therapy patients (65.7%) were at least 1% away from target of 7% at the time of intensification of therapy. Future studies should explore reasons behind this lack of earlier intensification and factors associated with clinical inertia. Disclosure G. Fernandes: None. B. Sawhney: Consultant; Self; Merck &amp; Co., Inc. H. Hannachi: Employee; Self; Merck &amp; Co., Inc. T. Wang: Employee; Spouse/Partner; Johnson &amp; Johnson. Employee; Self; Merck &amp; Co., Inc. A. McNeill: Employee; Self; Merck &amp; Co., Inc. K. Iglay: Employee; Self; Merck &amp; Co., Inc. Stock/Shareholder; Self; Merck &amp; Co., Inc. S. Rajpathak: None.

2352-PUB: Level of Glycemic Control in Type 2 Diabetes (T2D) Patients with Established Cardiovascular Disease (eCVD) or Chronic Kidney Disease (CKD) Prescribed an SGLT2i

The recent ADA/EASD consensus statement for management of hyperglycemia preferentially recommends the use of SGLT2i in patients with eCVD or CKD. However, no specific data exist on the level of glycemic control in this high-risk population currently receiving SGLT2i. Our study assessed glycemic control among adult T2D patients with eCVD/CKD on dual therapy (metformin+SGLT2i) at 3 different HbA1c targets (≥7%, ≥7.5%, ≥8%) using the GE Centricity Electronic Medical Record database (June 2015-June 2018). The index date was the most recent encounter for metformin+SGLT2i users. Patients were required to have ≥1 HbA1c measure in the 12 months prior to the index date and ≥1 year of medical history available. ECVD/CKD included patients with CVD only, CKD only, or both CVD and CKD. Results were examined in the overall study cohort and by subgroups of age, gender, and race. Of the 987 included study patients, 40% were female, median age was 62 years, and median A1c was 7.5%. Table 1 shows the level of glycemic control among the study population. 68%, 52% and 36% of patients had HbA1c ≥7%, ≥7.5%, and ≥8%, respectively. In conclusion, many patients with eCVD/CKD on dual therapy of metformin and SGLT2i were observed to have inadequate glycemic control and should be evaluated for medication adherence and further pharmacological intensification if appropriate. Disclosure K. Iglay: Employee; Self; Merck &amp; Co., Inc. Stock/Shareholder; Self; Merck &amp; Co., Inc. N. Bansal: Consultant; Self; Merck &amp; Co., Inc. T. Gulati: Consultant; Self; Merck &amp; Co., Inc. H. Hannachi: Employee; Self; Merck &amp; Co., Inc. G. Fernandes: None. S. Rajpathak: None.

1189-P: Effectiveness of Hydroxychloroquine (HCQ) 400 mg in Uncontrolled T2D Patients on Dual Therapy of Metformin and Sulfonylurea: A Real-World Experience in India

Objective: Many T2D patients have inadequate glycemic control despite conventional therapy of dual OHAs. Treating such patients in developing countries is a challenge as newer drugs are comparatively costly or patients may have apprehensions for injectable insulin. Objective of this observational study was to evaluate effectiveness of add-on therapy of HCQ in these patients. Methods: A prospective, observational, multi-centre study was conducted where 1,007 T2D patients (age between 18-65 years), uncontrolled on a combination of two OHAs, with HbA1c ≥7.5%, fasting blood glucose of ≥126 mg/dL or 2-hour blood glucose ≥200 mg/dL and body weight ≥60 kg were prescribed hydroxychloroquine sulphate 400 mg once daily for 24 weeks. Mean change in HbA1c, FBG, PPG, serum creatinine and lipid parameters were assessed. Results: At week 24, significant reduction in HbA1c (1.29%), FBG (18%), PPG (23%), TC (9%), LDL-C (12%) and non-HDL-C (12%) was observed (p &amp;lt; 0.0001). At the end of 24 weeks, 36.8% patients achieved HbA1c target of &amp;lt;7%. Conclusion: Hydroxychloroquine effectively improved glycemic and lipid parameters in uncontrolled T2D patients. It may emerge as a valuable therapeutic intervention for patients uncontrolled on two OHAs. Its beneficial effect on lipids may potentially translate to improved CV outcomes. Disclosure I. Purkait: Employee; Self; Ipca Laboratories Ltd. A. Pareek: Employee; Self; Ipca Laboratories Ltd. A. Panneerselvam: None. M.K. Mukhopadhyay: None. S. Kumar: Advisory Panel; Self; Abbott, Alere Inc., Alkem Laboratories, Eli Lilly and Company, Eris Lifesciences, Glenmark Pharmaceuticals Limited, Intas Pharmaceuticals Ltd., Johnson &amp; Johnson, Lupin Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi-Aventis, Sun Pharma, Torrent Pharma, USV Private Limited, Wockhardt, Zydus Pharmaceuticals, Inc. Consultant; Self; AstraZeneca, Biocon, Boehringer Ingelheim Pharmaceuticals, Inc., Dr. Reddys Laboratories. S.A. Chandratreya: None.

Comparison of efficacy of add-on therapy of teneligliptin versus pioglitazone among type 2 diabetes mellitus patients ineptly controlled on dual therapy of metformin plus sulfonylurea

Aim: The main aim of the study is to compare the efficacy of add-on therapy of teneligliptin (20 once daily) versus pioglitazone (15 mg once daily) among type 2 diabetes mellitus (T2DM) patients inadequately controlled on dual therapy of metformin (MF) plus sulfonylurea (SU). Materials and Methods: It is a prospective, observational, comparative study conducted in patients from the outpatient department of Sri Bhadrakali Hospital located at Warangal, Telangana state, India. The efficacy of pioglitazone and teneligliptin was assessed by measuring the change in the glycated haemoglobin (HbA1c), Fasting Plasma Glucose (FPG), Post Prandial Blood Glucose (PPBH) levels after 12 weeks of treatment. FPG, PPBG and HbA1c levels at baseline and 12 weeks. The primary endpoint was changed in HbA1c levels at 12 weeks as compared to the baseline levels in both groups. The secondary endpoints were changes in FPG, PPBG levels at 12 weeks as compared to baseline levels. Along with, serum cholesterol, triglycerides (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured both at baseline and after 12 weeks. Results: At study end, HbA1c levels were reduced from baseline by 0.7% (P = 0.0049) in the pioglitazone group and 1% (P = 0.0002) in the teneligliptin group. The mean changes in FPG levels from baseline to week 12 were −39.8 mg/dl (P ≤ 0.0001) in teneligliptin and −11.48 mg/dl (P = 0.00380) in pioglitazone group. The mean PPG levels from −47.8 mg/dl (P = 0.0003) in teneligliptin and −25.5 mg/dl (P = 0015) in pioglitazone group. After 12 weeks of study, the levels of TG, total cholesterol (TC), LDL −71.5 (P = 0.0973), −15 (P = 0.0501), 18.8 (P ≤ 0.0008) mg/dl and −31.38 (P ≤ 0.0001), −21 (P ≤ 0.0001), −11.68 (P = 0.0028) mg/dl in teneligliptin group and pioglitazone group, respectively. There was significant increase in HDL levels 5.3 (P ≤ 0.0001) mg/dl in teneligliptin group and 5.2 (P = 0.0001) mg/dl in pioglitazone group. Conclusion: Both teneligliptin 20 mg and Pioglitazone 15 mg provided additional HbA1c lowering to that achieved with MF and SU. Teneligliptin showed more effective reductions in HbA1c, FPG, PPBG, HDL and LDL levels. Pioglitazone showed significant changes in HbA1c, HDL, TC, triglyceride levels and significant changes in FPG, PPBG and LDL levels. Reduction in HbA1c and plasma lipids slows down the diabetes progression and decreases the risk of microvascular and macrovascular complications.

Mortality Risk of Noninsulin Glucose-Lowering Drugs in Type 2 Diabetes—A Network Meta-analysis of Observational Trials

Given the short-comings of randomized controlled trials, such as low numbers of patients and events, we aimed to perform a network meta-analysis of observational trials on the effects of non-insulin glucose-lowering drugs on all-cause and cardiovascular mortality in type 2 diabetes. We searched MEDLINE and EMBASE through August 2017. From the 38 eligible studies, we extracted patient characteristics, exposure, outcome, confounder-adjusted effect measures, and risk of bias. All-cause and cardiovascular mortality risk were assessed with random-effects network meta-analysis. In 32 studies reporting on all-cause mortality (1,661,945 persons) and in 11 studies on cardiovascular mortality (358,784 persons), 119,591 (7.2%) and 9,221 (2.6%) persons, respectively, died during follow-up. Compared to metformin, sulfonylurea drugs (SU) increased all-cause mortality risk (HR: 1.42 (95% CI: 1.29-1.56)). Dipeptidyl peptidase-4 inhibitors (DDP4i) added to metformin significantly decreased all-cause mortality risk compared to metformin monotherapy (HR: 0.76 (0.63-0.93)), any other drug class as monotherapy, and SU + metformin dual therapy (HR: 0.69 (0.60-0.79)). DPP-4i + metformin dual therapy was associated with even larger reductions in risk of cardiovascular mortality; HR: 0.40 (0.21-0.79) when compared to metformin monotherapy, and HR: 0.41 (0.23-0.74) when compared to SU + metformin dual therapy. Glucagon-like-peptide-1 receptor agonists + metformin dual therapy tended to, but did not significantly, decrease mortality risk when compared to metformin monotherapy (all-cause mortality, HR: 0.88 (0.53-1.47); cardiovascular mortality, HR: 0.74 (0.30-1.82)). In conclusion, this large network meta-analysis evidently confirmed that SU, compared to metformin, increased all-cause mortality risk. DPP-4i + metformin dual therapy, compared to other treatments, resulted in a consistent risk reduction of both all-cause and cardiovascular mortality. Disclosure B. Bongaerts: None. L.M. Lindner: None. A. Hoyer: None. O. Kuss: None. C. Herder: Other Relationship; Self; Sanofi, Eli Lilly and Company. H. Al-Hasani: None. K. Müssig: None. M. Roden: Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Research Support; Self; Boehringer Ingelheim GmbH. Consultant; Self; Poxel SA. Research Support; Self; Danone Nutricia Early Life Nutrition, GlaxoSmithKline plc., Nutricia Advanced Medical Nutrition, Sanofi. W. Rathmann: Advisory Panel; Self; AstraZeneca. Research Support; Self; Novo Nordisk A/S.

Characterization of Patients with Type 2 Diabetes (T2D) Who Discontinue DPP-4is following Insulin Initiation

While discontinuation of oral drugs, such as DPP-4i, at the time of insulin initiation is not uncommon, the characteristics associated with this discontinuation are not well understood. We conducted a retrospective database study using the Optum claims data to describe the prevalence of and factors associated with discontinuation of DPP-4i among patients on dual therapy of metformin and DPP-4i after initiating insulin. Our study included adult T2D patients on this dual therapy who initiated insulin (index) from Jan 2006-Sep 2015. 3,388 T2D patients met the study criteria; mean age: 62 years, 55% male, and 61% and 88% reported micro- and macrovascular complications, respectively. 32% (n=1086) of the study population discontinued DPP-4i therapy within 12 months after insulin initiation, with 1075 patients discontinuing in the first 3 months. Median time to discontinuation was 25 days (IQR 13-31 days). Available patient characteristics between continuers vs. discontinuers are described in TABLE. Data available from claims showed that patients who discontinue had higher out of pocket costs and higher proportion of renal and liver disease. Limitation of this study is lack of information on A1C and other clinical variables such as BMI. A Cox regression model will be employed to further investigate if these factors are predictive of discontinuation. Disclosure G. Fernandes: Employee; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; Janssen Research &amp; Development. Stock/Shareholder; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Spouse/Partner; Janssen Research &amp; Development. K. Iglay: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc. Z. Liu: Employee; Self; Merck &amp; Co., Inc. R. Shankar: Employee; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; NGM Biopharmaceuticals. I. Gantz: Employee; Self; Merck Sharp &amp; Dohme Corp. S. Rajpathak: Employee; Self; Merck &amp; Co., Inc..

Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Antidiabetes Agents in Different Baseline BMI Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: The real-world study of China PDS with 2083 type 2 diabetes mellitus (T2DM) patients showed that vildagliptin plus metformin (VM) therapy could effectively control the HbA1c with good tolerability. Here, we present the results of baseline BMI subgroups. Materials and Methods: In China PDS, T2DM patients with poor glycemic control on monotherapy were assigned to either VM dual therapy or other oral dual agents(OD) therapy according to local physician’s decision. For this analysis, patients were divided into three subgroups according to baseline BMI(&amp;lt;24kg/m2, 24-28kg/m2, &amp;gt;28kg/m2). The primary outcome was the proportion of patients with HbA1c&amp;lt;7% and without tolerability events(hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included mean changes in HbA1c from baseline to study endpoint and tolerability. Results: In total, 389(149 in VM vs. 240 in OD) patients in BMI&amp;lt;24kg/m2 group, 625(304 in VM vs. 321 in OD) patients in BMI 24-28kg/m2 group, and 260(151 in VM vs. 109 in OD) patients in BMI&amp;gt;28kg/m2 group were enrolled. Compared with OD, significantly higher proportion patients reached primary outcome in VM in BMI&amp;lt;24kg/m2 group (47.0% vs. 35.0%; P=0.019), in BMI 24-28kg/m2 group (52.6% vs. 33.3%; P&amp;lt;0.001), and in BMI&amp;gt;28kg/m2 group (51.0% vs. 33.9%; P=0.006). Mean HbA1c changes were significantly greater in VM than in OD(BMI&amp;lt;24kg/m2: -1.23% vs. -0.76%; BMI 24-28kg/m2: -1.32% vs. -0.79%; BMI&amp;gt;28kg/m2: -1.29% vs. -0.84%; P&amp;lt;0.for all). VM resulted in less tolerability findings than OD in BMI&amp;lt;24kg/m2 (11.4% vs. 19.2) and BMI 24-28kg/m2 (3.6% vs. 14.6%) groups (P&amp;lt;0.for both), but not in BMI &amp;gt;28kg/m2 group (4.6% vs. 5.5%, P&amp;gt;0.05). Conclusion: In different baseline BMI groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and was well tolerated compared with OD. Disclosure H. Jin: None. Y. Han: None. L. Chen: None. D. Hu: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Antidiabetes Agents in Different Baseline HbA1c Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: China PDS aimed to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). Here, we present the results of prespecified baseline HbA1c subgroups. Materials and Methods: In China PDS, T2DM patients with poor glycemic control by monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this subgroup study, patients were divided into three groups according to their baseline HbA1c levels (≤8%, 8-9%, &amp;gt;9%). The primary outcome was the proportion of patients with HbA1c&amp;lt;7% and without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included mean changes in HbA1c from baseline to study endpoint and tolerability. Results: In total, 7(312 in VM vs. 394 in OD) patients in HbA1c≤8% group, 332 (151 in VM vs. 181 in OD) patients in HbA1c 8-9% group, and 236 (141 in VM vs. 95 in OD) patients in HbA1c&amp;gt;9% group were enrolled. Compared with OD, significantly higher proportion of patients reached primary outcome with VM in HbA1c ≤8% group (57.4% vs. 38.3%, P&amp;lt;0.001), in HbA1c 8-9% group (39.7% vs. 26.0%, P=0.008), and in HbA1c&amp;gt;9% group (48.2% vs. 31.6%, P=0.011). The mean HbA1c changes from baseline to study endpoint in VM and OD were -0.61±0.932 and -0.32±0.874 (P&amp;lt;0.001) in HbA1c≤8% group, -1.37±1.072 and -0.97±1.169 (P&amp;lt;0.001) in HbA1c 8-9% group, and -2.71±1.392 and -2.39±1.4(P=0.305) in HbA1c&amp;gt;9% group. Compared with OD, VM resulted in less tolerability findings (HbA1c≤8%: 7.7% vs. 16.8%; HbA1c 8-9%: 2.6% vs. 9.4%; HbA1c&amp;gt;9%: 5.0% vs. 16.8%; P&amp;lt;0.for all). Conclusion: In different baseline HbA1c groups, vildagliptin plus metformin dual therapy was associated with better glycemic control and good tolerability. Disclosure D. Hu: None. Y. Han: None. L. Chen: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Effectiveness and Tolerability of Vildagliptin plus Metformin Dual Therapy Compared with Insulin Secretagogue plus Metformin Dual Therapy in Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: The China PDS aims to investigate the effectiveness and safety of vildagliptin dual therapy in type 2 diabetes mellitus (T2DM) patients. Here, we compared the vildagliptin plus metformin (VM) and insulin secretagogue plus metformin (ISM). Materials and Methods: China PDS was a prospective, 1-year, real-world study conducted in 52 sites in patients with T2DM and inadequately controlled on monotherapy. Eligible patients were assigned either vildagliptin dual therapy or other dual therapy according to local physician’s decision. The proportions of patients with HbA1c&amp;lt;7%, without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event), and tolerability were compared in VM and ISM in this study. Results: In total, 933 patients received vildagliptin dual therapy with 64.7% for VM, while 670 patients received other dual therapy with 48.7% for ISM (Table 1). Compared with ISM (31.6%), VM (50.8%) had higher proportion of patients reaching the primary outcome (P&amp;lt;0.001; adjusted OR, 2.14; 95% CI, 1.59-2.87). VM (5.8%) had less tolerability events than ISM (16.4%) (RR, 0.386; 95% CI, 0.26-0.58). Conclusion: China PDS demonstrates that in a real-life setting, VM was effective in glycemic control and was well tolerated when compared with ISM. Disclosure L. Chen: None. Y. Han: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. L. Zang: None. M. Liu: None. J. He: None. Y. Mu: None.

Effectiveness and Tolerability of Vildagliptin plus Metformin Compared with Other Oral Dual Agents in Different Regional Patients with Type 2 Diabetes—A Real-World Study (China PDS)

Background and Aim: China PDS aims to investigate the real-world effectiveness and tolerability of vildagliptin plus metformin (VM) in patients with type 2 diabetes mellitus (T2DM), compared with other oral dual agents (OD). In this study, we present the results of different regional subgroup analysis. Materials and Methods: In China PDS, T2DM patients with inadequate glycemic control on monotherapy were assigned to either VM dual therapy or OD therapy according to local physician’s decision. In this prespecified subgroup study, patients were divided into three groups according to their geographic regions (East China, North China, and South China). The primary outcome was the proportion of patients with HbA1c&amp;lt;7% and without tolerability events (hypoglycemia, weight gain, or discontinuation due to gastrointestinal event) at 12th month. Secondary outcomes included the HbA1c change from baseline to study endpoint, and tolerability. Results: In total, 357 (126 in VM vs. 231 in OD) patients in East China, 499 (292 in VM vs. 207 in OD) patients in North China, and 65 (27 in VM vs. 38 in OD) patients in South Chinawere enrolled. Compared with OD, significantly higher proportion of VM treated patients achieved primary outcome in East China (49.2% vs. 28.1%, P &amp;lt;0.001), North China (52.1% vs. 39.1%, P=0.004), and in South China (66.7% vs. 36.8%, P=0.018). Mean HbA1c changes were significantly greater in VM than in OD in East China (-1.24% vs. -0.55%, P&amp;lt;0.001) and North China groups (-1.35% vs. -0.93%, P=0.011), but not in South China group (-2.12% vs. -1.31%, P=0.147). VM resulted in less tolerability findings than OD in East China (6.3% vs. 18.2) and North China (6.5% vs. 15.0%) groups (P&amp;lt;0.for both), but not in South China group (3.7% vs. 26.3%, P&amp;gt;0.05). Conclusion: In all regional subgroups, vildagliptin plus metformin dual therapy was generally associated with good glycemic control and was well tolerated. Disclosure L. Zang: None. Y. Han: None. L. Chen: None. D. Hu: None. H. Jin: None. N. Yang: None. X. Shi: None. Q. Li: None. L. Liang: None. M. Liu: None. J. He: None. Y. Mu: None.

Prescription of oral antidiabetic drugs in Tyrol - Data from the Tyrol diabetes registry 2012-2015.

SummaryDiabetes mellitus affects 9% of the adult population worldwide and the economic burden of the disease is growing exponentially. In type 2 diabetes mellitus (T2DM), when life style interventions fail to achieve treatment targets, oral antidiabetic drugs are prescribed to improve glycemic control. Several new oral antidiabetics have been launched in the last few years, which enlarged the spectrum of available treatment options in T2DM. The present study aimed to examine T2DM treatment patterns in a cohort of 7769 patients recruited from the Diabetes Registry Tyrol (DRT) with at least one visit from 2012–2015. Secondly, the study aimed to evaluate the use of new oral antidiabetics compared to older oral antidiabetics (OAD). It was found that 43.4% of all patients were treated with OAD alone while 21.2% had oral antidiabetics combined with insulin. 19.9% of the study population were treated with insulin or insulin analogs only. 15.3% had no pharmacological treatment. Metformin was used most frequently (47.9% of the study population), followed by gliptines (27.2%). The most common treatment regimen in this population was the dual therapy of metformin and another OAD (17.2%), followed by metformin monotherapy (16.6%) and triple therapy of metformin and two additional OAD (11.0%).

Progression to insulin therapy among patients with type 2 diabetes treated with sitagliptin or sulphonylurea plus metformin dual therapy.

AimTo assess time to insulin initiation among patients with type 2 diabetes mellitus (T2DM) treated with sitagliptin versus sulphonylurea as add‐on to metformin.MethodsThis retrospective cohort study used GE Centricity electronic medical records and included patients aged ≥18 years with continuous medical records and an initial prescription of sitagliptin or sulphonylurea (index date) with metformin for ≥90 days during 2006–2013. Sitagliptin and sulphonylurea users were matched 1 : 1 using propensity score matching, and differences in insulin initiation were assessed using Kaplan–Meier curves and Cox regression. We used conditional logistic regression to examine the likelihood of insulin use 1–6 years after the index date for each year.ResultsPropensity score matching produced 3864 matched pairs. Kaplan–Meier analysis showed that sitagliptin users had a lower risk of insulin initiation compared with sulphonylurea users (p = 0.003), with 26.6% of sitagliptin users initiating insulin versus 34.1% of sulphonylurea users over 6 years. This finding remained significant after adjusting for baseline characteristics (hazard ratio 0.76, 95% confidence interval 0.65–0.90). Conditional logistic regression analyses confirmed that sitagliptin users were less likely to initiate insulin compared with sulphonylurea users [odds ratios for years 1–6: 0.77, 0.79, 0.81, 0.57, 0.29 and 0.75, respectively (p < 0.05 for years 4 and 5)].ConclusionsIn this real‐world matched cohort study, patients with T2DM treated with sitagliptin had a significantly lower risk of insulin initiation compared with patients treated with sulphonylurea, both as add‐on to metformin.