Failing Metformin Monotherapy Research Articles

A transparent machine learning algorithm uncovers HbA1c patterns associated with therapeutic inertia in patients with type 2 diabetes and failure of metformin monotherapy

AimsThis study aimed to identify and categorize the determinants influencing the intensification of therapy in Type 2 Diabetes (T2D) patients with suboptimal blood glucose control despite metformin monotherapy. MethodsEmploying the Logic Learning Machine (LLM), an advanced artificial intelligence system, we scrutinized electronic health records of 1.5 million patients treated in 271 diabetes clinics affiliated with the Italian Association of Medical Diabetologists from 2005 to 2019. Inclusion criteria comprised patients on metformin monotherapy with two consecutive mean HbA1c levels exceeding 7.0%. The cohort was divided into “inertia-NO” (20,067 patients with prompt intensification) and “inertia-YES” (13,029 patients without timely intensification). ResultsThe LLM model demonstrated robust discriminatory ability among the two groups (ROC-AUC = 0.81, accuracy = 0.71, precision = 0.80, recall = 0.71, F1 score = 0.75). The main novelty of our results is indeed the identification of two main distinct subtypes of therapeutic inertia. The first exhibited a gradual but steady HbA1c increase, while the second featured a moderate, non-uniform rise with substantial fluctuations. ConclusionsOur analysis sheds light on the significant impact of HbA1c levels over time on therapeutic inertia in patients with T2D, emphasizing the importance of early intervention in the presence of specific HbA1c patterns.

Effects of dapagliflozin compared with glimepiride on body composition in Asian patients with type 2 diabetes inadequately controlled with metformin: The BEYOND study.

To evaluate the effect of dapagliflozin on body composition such as total body fat (BF) mass, abdominal visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) areas compared with glimepiride in Korean patients with type 2 diabetes. This was a 52-week, multicentre, randomized, parallel-group, open-label, Phase IV (NCT02564926) study. Patients with inadequate glycaemic control (glycated haemoglobin ≥7.0% and <10.0%) on metformin monotherapy (≥1000 mg/day) were randomized 1:1 to receive dapagliflozin 10 mg/day or glimepiride 1-2 mg/day for 12 months as an add-on to metformin. Baseline and end of study body composition evaluations included dual-energy X-ray absorptiometry and abdominal computed tomography scans. Of 124 enrolled patients from 14 centres, 121 received study treatment (dapagliflozin: 60; glimepiride: 61) and 106 (85.5%) completed the study. Over 52 weeks, the dapagliflozin group showed the following differences versus the glimepiride group: -2.59 kg BF mass, -1.94% BF%, -17.55 cm2 VAT area, -18.39 cm2 SAT area, -0.46% glycated haemoglobin, -18.25 mg/dl fasting blood glucose, -3.7 kg weight, -2.21 cm waist circumference, -1.37 kg/m2 body mass index, -6.81 mmHg systolic blood pressure and +657.71 ng/ml in adiponectin; all were statistically significant. Both groups had similar incidences of adverse events; however, hypoglycaemic events were mainly (12 of 15) reported in the glimepiride group. Dapagliflozin reduced total BF mass, abdominal VAT and SAT areas, and showed better glycaemic control than glimepiride. Being safe and well-tolerated, dapagliflozin appears to be a more favourable alternative to sulphonylureas as add-on therapy after metformin monotherapy failure in Korean patients with type 2 diabetes.

Evaluating gliclazide for the treatment of type 2 diabetes mellitus

ABSTRACT Introduction Sulfonylureas have been the standard second-line treatment after failure of metformin monotherapy in patients with type 2 diabetes (T2D) but they are becoming less popular as the newer glucose lowering agents have relatively lower risk of hypoglycemia and some of them have been shown to reduce cardiovascular and renal events. Gliclazide differs from other sulfonylureas in several respects and may provide a suitable option for some patients with T2D. Areas covered In this article we review the pharmacokinetics, pharmacodynamics and clinical efficacy of gliclazide based on the available literature. Expert opinion Gliclazide in the modified release (MR) formulation given once daily provides good 24-hour glycemic efficacy comparable to most other groups of glucose lowering drugs. Hypoglycemic events are less frequent than with some other sulfonylureas and weight gain is not a major problem. Cardiovascular outcome studies have shown no evidence of increased cardiovascular events with gliclazide and the durability of glucose lowering effects is comparable to other drug groups. Lower doses of gliclazide appear to have an incretin enhancing effect and overall it can provide a cost-effective treatment that is useful in many patients.

Predictors of metformin monotherapy failure in gestational diabetes mellitus.

Objective Metformin has emerged as a safe and effective pharmacological alternative to insulin in gestational diabetes mellitus (GDM), being associated with lower maternal weight gain and hypoglycemia risk. Nevertheless, glycemic control is unaccomplished in a considerable proportion of women only treated with metformin. We aim to determine the metformin monotherapy failure rate in GDM and to identify predictors of its occurrence.Design and methodsThis was a retrospective multicenter study including pregnant women with GDM patients who started metformin as a first-line pharmacological treatment (n = 2891). A comparative analysis of clinical and analytical data between the group of women treated with metformin monotherapy and those needing combined therapy with insulin was performed.ResultsIn 685 (23.7%) women with GDM, combined therapy to achieve adequate glycemic control was required. Higher pregestational BMI (OR 1.039; CI 95% 1.008–1.071; P-value = 0.013), higher fasting plasma glucose (PG) levels in oral glucose tolerance test (OGTT) (OR 1.047; CI 95% 1.028–1.066; P-value <0.001) and an earlier gestational age (GA) at metformin introduction (0.839; CI 95% 0.796–0.885, P-value < 0.001) were independent predictive factors for metformin monotherapy failure. The best predictive cutoff values were a fasting PG in OGTT ≥87 mg/dL and GA at metformin introduction ≤29 weeks.ConclusionsIn 685 (23.7%) women, combined therapy with insulin to reach glycemic control was required. Higher pre-gestational BMI, fasting PG levels in OGTT ≥87 mg/dL and introduction of metformin ≤29 weeks of GA were independent predictive factors for metformin monotherapy failure. The early recognition of these characteristics can contribute to the establishment of individualized therapeutic strategies and attain better metabolic control during pregnancy.

Secondary metformin monotherapy failure in individuals with type 2 diabetes mellitus

IntroductionTo assess secondary metformin monotherapy (MM) failure in a real-world type 2 diabetes mellitus (T2DM) cohort.Research design and methodsUsing the IQVIA Electronic Medical Record (formerly GE Centricity) database, adults with...

Efficacy of metformin monotherapy in US veterans with type 2 diabetes and preexisting chronic kidney disease stage 3

To evaluate the glycaemic efficacy of metformin in people with type 2 diabetes (T2D) and stage 3 chronic kidney disease (CKD3). This was a retrospective study including 145980 US veterans with T2D and an estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m2 who initiated metformin monotherapy between November 1999 and July 2017. Propensity-score-matched cohorts were generated based on baseline variables associated with CKD3 (eGFR 30-59 mL/min/1.73 m2 ) to evaluate the independent association between CKD3 and metformin discontinuation, the addition of a second hypoglycaemic agent, and changes in glycated haemoglobin (HbA1c) from baseline in those with and without CKD3. Associations were examined using the Kaplan-Meier method and multivariable regression models, adjusted for baseline and 12-month average metformin dose. The mean age of the entire cohort was 60.7 years, and 95% of the cohort were men, 21% were African American and 9% had CKD3. In the adjusted analyses, patients with CKD3 had a higher risk of metformin discontinuation or addition of a second hypoglycaemic agent, as compared with patients without CKD (hazard ratio [HR] 1.22, 95% confidence interval [CI] 1.19-1.26, and HR 1.26, 95% CI 1.13-1.40, respectively). Among metformin monotherapy users, there were no differences in the average HbA1c reduction from baseline to 12 or 24 months between patients with and without CKD3. Individuals with CKD3 and T2D were at increased risk of metformin monotherapy failure. However, the HbA1c-lowering efficacy of metformin was similar in patients with and without CKD3, highlighting that metformin is a valuable treatment option for newly treated individuals with T2D and CKD3.

Preexisting CKD Increases Risk of Metformin Monotherapy Failure in US Veterans with Type 2 Diabetes

Preexisting CKD Increases Risk of Metformin Monotherapy Failure in US Veterans with Type 2 Diabetes

Glucagon-like peptide 1 agonists for treatment of patients with type 2 diabetes who fail metformin monotherapy: systematic review and meta-analysis of economic evaluation studies

ObjectivesTo conduct a systematic review and meta-analysis and to pool the incremental net benefits (INBs) of glucagon-like peptide 1 (GLP1) compared with other therapies in type 2 diabetes mellitus (T2DM)...

Distance to glycemic goal at the time of treatment intensification in patients with type 2 diabetes mellitus failing metformin monotherapy in the United States

Background: A substantial proportion of patients with type 2 diabetes mellitus (T2DM) do not reach their target HbA1c level on metformin. The objective of this retrospective observational cohort study is to better characterize the distance between HbA1c target and patient’s actual HbA1c level (the distance to goal), using a target HbA1c of 7.0% (53 mmol/mol), in patients with T2DM who have started metformin monotherapy.Methods: We used data from the GE Centricity Electronic Medical Record database by IQVIA in 2016 in the United States (US) to identify adults with T2DM who started metformin monotherapy (MM) and received at least 90 days of treatment. Patients were categorized into three groups: those who achieved the goal of HbA1c <7.0%, those who did not achieve the goal of HbA1c <7.0% (i.e. failed MM) and received intensified treatment, and those who failed MM and did not receive intensified treatment. Distance to goal was computed for patients in each group.Results: We identified 20,704 patients in the US database who started MM; 1741 (8.4%) failed MM and received intensified treatment, while 4977 (24.0%) failed MM and did not receive intensified treatment. The mean post-MM HbA1c for those who failed MM and received intensified treatment was 8.7% (72 mmol/mol) (median 8.2%, 66 mmol/mol) and the mean distance to goal was 1.7% (median 1.2%). The mean post-MM HbA1c for those who failed MM and did not receive intensified treatment was 8.0% (64 mmol/mol) (median 7.5%, 58 mmol/mol) and the mean distance to goal was 1.0% (median 0.5%).Conclusion: A proportion of US T2DM patients do not achieve glycemic control (target HbA1c < 7.0%) despite 90 days of MM. Patients who failed MM and eventually received intensified treatment did so when their HbA1c distance to goal exceeded the level at which one add-on therapy alone might be sufficient to bring them to goal.

Predictive Factors of Successful Treatment of Gestational Diabetes with Metformin Monotherapy

Objective: To evaluate the factors affecting the success of metformin in management of GDM. Methods: A prospective cohort study was done for 94 patients diagnosed with GDM from April 2019 to March 2020 who needed pharmacological treatments in addition to diet and lifestyle modification. Cases treated with metformin monotherapy were compared with others who needed insulin in addition to metformin for glycemic control. Patient characteristics, glycemic control data and neonatal outcome were evaluated. Univariate and multivariate analysis was done to find the independent factors affecting the success of metformin. Results: Of 94 patients with GDM who needed pharmacological treatment, 73 (77.6%) used only metformin for treatment of GDM and 21 (22.4%) needed insulin to be added to metformin. Multivariate analysis revealed that BMI was the only significant factor that affects the success of metformin alone in control of GDM (p = 0.03). ROC curve of BMI showed that the cut off value of the highest sensitivity is 32.1 above which metformin monotherapy failed to control GDM. Conclusion: Metformin can be considered as a safe and effective drug for treatment of GDM. Obesity was found as a predictive factor for failure of metformin monotherapy.

SGLT2 inhibitor or GLP-1 receptor agonist in type 2 diabetes?

Among the newest glucose-lowering agents for the treatment of type 2 diabetes, two classes raise much interest: glucagon-like peptide-1 (GLP-1) receptor agonists and sodium-glucose cotransporter type 2 (SGLT2) inhibitors. Indeed, both showed a cardiovascular protection in dedicated outcome studies in patients with type 2 diabetes at high cardiovascular risk. 1 Scheen AJ Cardiovascular outcome studies in type 2 diabetes: comparison between SGLT2 inhibitors and GLP-1 receptor agonists. Diabetes Res Clin Pract. 2018; 143: 88-100 Summary Full Text Full Text PDF PubMed Scopus (35) Google Scholar , 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar These findings had a major effect on the newer guidelines for the management of type 2 diabetes. In patients with atherosclerotic cardiovascular disease, guidelines now recommend, after failure of metformin monotherapy, the addition of a GLP-1 receptor agonist or an SGLT2 inhibitor that was shown to reduce the risk of major cardiovascular events. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar In the absence of heart failure or renal disease, two conditions in which SGLT2 inhibitors appear more protective, 2 Zelniker TA Wiviott SD Raz I et al. Comparison of the effects of glucagon-like peptide receptor agonists and sodium-glucose cotransporter 2 inhibitors for prevention of major adverse cardiovascular and renal outcomes in type 2 diabetes mellitus. Circulation. 2019; 139: 2022-2031 Crossref PubMed Scopus (273) Google Scholar the clinician can choose between these two pharmacological options without specific guidance in the absence of comparative trials. 3 Davies MJ D'Alessio DA Fradkin J et al. Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2018; 61: 2461-2498 Crossref PubMed Scopus (604) Google Scholar Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trialOnce-weekly semaglutide 1·0 mg was superior to daily canagliflozin 300 mg in reducing HbA1c and bodyweight in patients with type 2 diabetes uncontrolled on metformin therapy. These outcomes might guide treatment intensification choices. Full-Text PDF

What Next After Metformin? Thinking Beyond Glycaemia: Are SGLT2 Inhibitors the Answer?

The prevalence of type 2 diabetes continues to increase, along with a proliferation of glucose-lowering treatment options. There is universal agreement in the clinical community for the use of metformin as the first-line glucose-lowering therapy for the majority of patients. However, controversy exists regarding the choice of second-line therapy once metformin is no longer effective. The most recent treatment consensus focuses on the presence of cardiovascular disease, heart failure or kidney disease as a determinant of therapy choice. The majority of patients in routine practice, however, do not fall into such categories. Heart failure and kidney disease represent significant clinical and cost considerations in patients with type 2 diabetes and have a close pathophysiological association. Recent data has illustrated that sodium-glucose transporter 2 (SGLT2) inhibitor therapy can reduce the burden of heart failure and the progression of renal disease across a wide range of patients including those with and without established disease, supported by an increased understanding of the mechanistic effects of these agents. Furthermore, there is growing evidence to illustrate the overall safety profile of this class of agents and support the benefit–risk profile of SGLT2 inhibitors as a preferred option following metformin monotherapy failure, with respect to both kidney disease progression and heart failure outcomes.

1143-P: Secondary Metformin Monotherapy Failure in Type 2 Diabetes Mellitus Patients

Clinical guidelines recommend metformin monotherapy (MM) as an initial glucose-lowering therapy for type 2 diabetes (T2D) patients [pts]. While studies have previously reported the incidence of metformin monotherapy failure, there are limited data specifically assessing the rate of “secondary” MM failure (defined as loss of control following initial achievement of glycemic control). The current study sought to characterize and evaluate factors associated with secondary failure among T2D pts on MM in a diverse U.S. population. Using the GE Centricity Electronic Medical Record database, we conducted a retrospective study of T2D pts ≥18 years initiating MM between 1/2013-5/2016 and achieving an HbA1c &amp;lt;7% (index date) within 6 months of initiation. Secondary MM failure was assessed at 6, 12, 18, and 24 months after index date and was defined based on HbA1c ≥7% or by treatment change (therapy switch or add-on intensification). Multivariable logistic regression was used to evaluate the factors associated with secondary MM failure. Of 4,775 pts included, 53.4% were female, the median age was 63 years and median HbA1c at index date was 6.4%. At 6 months, the proportion of pts who experienced MM failure by HbA1c ≥7% was 9.76% and by treatment change was 6.01%. At 12, 18 and 24 months, these proportions (%) were 16.20/8.00, 22.95/9.36, and 28.82/10.68, respectively. Factors positively associated with secondary MM failure (HbA1c ≥7%) at 24 months were male gender, HbA1c at index date and younger age (&amp;lt;65 years). These data suggest that after initially achieving an A1C &amp;lt;7%, a substantial proportion of pts on MM experience secondary failure within a relatively short period of time, with an increasing number experiencing failure within 2 years. Pts controlled on MM may benefit from regular HbA1c testing to ensure timely treatment modification. Further studies assessing whether initial metformin combination therapy would result in more durable glycemic control would also be of value. Disclosure T. Weiss: Employee; Self; Merck &amp; Co., Inc. K. Iglay: Employee; Self; Merck &amp; Co., Inc. Stock/Shareholder; Self; Merck &amp; Co., Inc. P. Verma: None. S. Rajpathak: None. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck &amp; Co., Inc. L. Blonde: Consultant; Self; Gilead Sciences, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. Research Support; Self; Janssen Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi US. Speaker's Bureau; Self; Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi US.

1495-P: Distance to Glycemic Target of Patients (Pts) with Type 2 Diabetes (T2D) and Established Cardiovascular Disease (eCVD) and/or Chronic Kidney Disease (CKD) Failing Metformin Monotherapy in the U.S.

Previous studies have shown that a large proportion of pts with T2D are not at glycemic target, but the distance to target is not well characterized, including among high risk patients such as those with eCVD/CKD. The objective of the study was to assess the distance to glycemic target by eCVD/CKD status. This retrospective study using GE Centricity Electronic Medical Record database (2016 data) included adult T2D pts on metformin monotherapy with ≥12 months of enrollment prior to index date (initiation of metformin) and prescribed an add-on agent. Distance to target was calculated as median difference from 3 HbA1c targets: &amp;lt;7%, &amp;lt;7.5% and &amp;lt;8%. Of the 1741 included pts, mean age was 57 years, 49% were female, 25% had eCVD/CKD. Table shows the distance to glycemic targets by eCVD/CKD status. Median difference from target ranged from 0.2%-1.2% depending on the specified threshold. 44.6%, 33.6% and 25.6% of pts were ≥1.5% away from targets of 7%, 7.5% and 8%, respectively, at time of add-on therapy. Difference from target and proportion of pts ≥1.5% from target was even higher for those without compared to with eCVD/CKD. In conclusion, a significant proportion of pts on metformin are more than 1.0% away from glycemic targets at the time of intensification and those without eCVD/CKD are likely to be intensified at much higher HbA1c. 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.

Ten years of experience with DPP-4 inhibitors for the treatment of type 2 diabetes mellitus.

Achieving and maintaining recommended glycemic targets without causing adverse e ffects, including hypoglycemia, is challenging, especially in older patients with type 2 diabetes mellitus (T2DM). The introduction of dipeptidyl peptidase-4 (DPP-4) inhibitors, more than 10years ago, has provided an alternative to conventional medications for the intensification of glucose-lowering treatment after failure of metformin monotherapy, and therefore, marked an important advance in the management of T2DM. By prolonging the activity of incretin hormones, DPP-4 inhibitors induce insulin release and decrease glucagon secretion in a glucose-dependent manner. This results in a more physiologic glycemic control as compared to that ensured by insulin secretagogues (sulfonylureas and glinides). Overall, DPP-4 inhibitors have a favorable safety profile and can be used without dose adjustments in older adults and in patients with mild renal impairment; they have a neutral effect on body weight and do not cause hypoglycemia by themselves. Safety issues, reported mainly in post-marketing surveillance programs and including cardiovascular outcomes and the risk of acute pancreatitis, are being extensively investigated. The aim of this review is to discuss the impact of DPP-4 inhibitors on the treatment of T2DM, after 10years of experience, with an emphasis on diabetes care in Italy. We will first describe T2DM treatment in Italy and then provide an overview of the main findings from randomized controlled trials, real-world studies and post-marketing surveillance programs with DPP-4 inhibitors.

Impact of Early Intensification with Sitagliptin on Glycemic Goal Attainment among Patients with Metformin Monotherapy Failure

Background: Delay in the intensification of type 2 diabetes (T2DM) treatment after metformin monotherapy failure, or clinical inertia, is often observed among patients with poor glycemic control. Sitagliptin is used frequently as an add-on to metformin monotherapy among patients with T2DM. The objective of the study is to evaluate the association between early treatment intensification with sitagliptin and glycemic goal attainment among patients failing metformin monotherapy. Methods: This retrospective database study of adult T2DM patients was conducted using the Quintiles Electronic Medical Record (EMR) database. The study population consisted of patients diagnosed with T2DM who failed to achieve A1c level of &amp;lt;7% on metformin monotherapy between January 20and June 2015. The study included two groups (1) those who did not receive treatment intensification within 3 months after metformin failure (non-early group), but were intensified with any oral anti-hyperglycemic agent between 4 and 12 months and (2) those who were intensified with sitagliptin within 3 months (early sitagliptin group). A Cox regression analysis was conducted to evaluate the association between sitagliptin use and A1c goal attainment within 12 months. Results: We identified 2,852 patients aged ≥18 years with T2DM who failed metformin monotherapy, of which 362 patients were intensified with sitagliptin within 3 months and 2,490 patients were included in the non-early group. A multivariate Cox regression model adjusted for age, gender, BMI, smoking status, baseline A1c, comorbidities, and other nondiabetic medications showed that early sitagliptin therapy resulted in doubling the likelihood of achieving A1c goal attainment (HR 2.12; 95% CI 1.80-2.50) within 12 months compared to non-early group. Conclusion: Early intensification with sitagliptin results in higher goal achievement levels among patients failing metformin monotherapy failure. Disclosure F. Ejzykowicz: Employee; Self; Merck Sharp &amp; Dohme Corp. J. Liu: Employee; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. S.S. Engel: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc. S. Rajpathak: Employee; Self; Merck &amp; Co., Inc..

Distance from Glycemic Target at the Time of Add-On Initiation in Patients with Type 2 Diabetes (T2D) Failing Metformin Monotherapy in the United States

While it is known that a substantial proportion of U.S. patients with T2D are not at glycemic target, the distance to glycemic target has not been adequately characterized, especially at the time of add-on initiation. The objective of the study was to quantify the distance from an HbA1c target of 7% among patients failing metformin monotherapy at the time of treatment intensification with an add-on agent. This retrospective study using Quintiles Electronic Medical Record database included patients with diagnosed T2DM on metformin monotherapy between Jan 2012- Dec 2014 (index date), with at least 12 months of continuous enrollment pre-index date, documented HbA1c ≥7% and prescribed an add-on agent. Patients with type 1 diabetes, pregnancy/gestational diabetes or other secondary diabetes were excluded. Distance from glycemic target was calculated as the median difference of HbA1c from target of 7% at the time of add-on initiation was reported. A total of 22,239 T2DM patients met the study criteria; mean age of 58.3 years, 51.2% were female, 10.8% of patients had a history of microvascular complications; 5.1% had a history of macrovascular complications. Median difference from HbA1c target was 1.3%, with 23.7% (n=5261) of patients between 1 to 2%, and 35.5% (n=7897) greater than 2% from HbA1c target of 7%. In a sensitivity analysis that excluded patients for whom HbA1c target higher than 7% may be more appropriate (older patients ≥75 years, those with chronic diabetes complications or history of hypoglycemia; n = 5195) this distance to goal was still as high as 1.4%. In these patients, where a target of 8% may be more appropriate, 27.0% were ≥1% away from the target at the time of intensification. In this study, we found more than half of the metformin monotherapy patients were at least 1% away from glycemic target of 7% at the time of add-on initiation. 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. H. Hannachi: Employee; Self; Merck &amp; Co., Inc. J. Liu: Employee; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; Anthem, Inc.. Employee; Self; Janssen Scientific Affairs, LLC. T. Wang: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc.. Employee; Spouse/Partner; Janssen Pharmaceuticals, Inc. A. McNeill: Employee; Self; Merck &amp; Co., Inc.. Stock/Shareholder; Self; Merck &amp; Co., Inc.. A.Z. Fu: None. S. Rajpathak: Employee; Self; Merck &amp; Co., Inc..

Cost Effectiveness of DPP-4i and SGLT2i Combination Therapy for the Treatment of Type 2 Diabetes in the U.S.

Management of type 2 diabetes (T2D) needs different treatment strategies to achieve the individualized glycemic goal. This study evaluated the long-term cost effectiveness of strategies involving pathway 1: metformin followed by intensification with dipeptidyl peptidase-4 inhibitors (DPP-4i), sodium-glucose co-transporter 2 inhibitors (SGLT2i) and insulin vs. pathway 2: metformin followed by intensification with sulfonylurea (SU) and insulin in the U.S. Cost-effectiveness analysis was performed using the validated QuintilesIMS CORE Diabetes Model from a U.S. payer perspective. Clinical and economic outcomes were modeled over a lifetime for a cohort of T2D patients who fail to achieve glycemic goal on metformin monotherapy. Clinical data were obtained from clinical trials. Direct medical costs [e.g., medications (whole sale acquisition costs), diabetes management, adverse events, and complications] were obtained from published sources. Despite higher direct medical costs for pathway 1 compared to pathway 2 ($117,779 vs. $93,196 respectively); pathway 1 improved total quality-adjusted life years (QALY) by 0.28 vs. pathway 2. Pathway 1 also led to cost offsets from fewer diabetes-related complications and delayed initiation of insulin. The incremental cost-effectiveness ratio (ICER) was favorable for pathway 1 at $89,038/QALY. Most of the scenario analysis (changes in treatment effect, hypoglycemia, and cardiovascular protective effects of SGLT2is) resulted in ICERs under $100,000/QALY except for the population with baseline HbA1c of 7%, and older age (65+ years). Negotiated discounts on branded medications resulted in significant improvement in ICERs (ICER of $69,554/QALY for 15% discount and $0/QALY for 75% discount). Among patients failing metformin monotherapy in the U.S, additional intensification with DPP-4i followed by SGLT2i may be considered more cost effective compared to intensification with SU followed by insulin. Disclosure M. Pawaskar: Employee; Self; Merck &amp; Co., Inc. S. Bilir: Consultant; Self; Merck &amp; Co., Inc.. A. Graber-Naidich: None. C.D. Gonzalez: Employee; Self; Merck &amp; Co., Inc. S. Rajpathak: Employee; Self; Merck &amp; Co., Inc. G.M. Davies: Employee; Self; Merck &amp; Co., Inc..

Clinical Inertia in Type 2 Diabetes Management: Evidence From a Large, Real-World Data Set

Despite clinical practice guidelines that recommend frequent monitoring of HbA1c (every 3 months) and aggressive escalation of antihyperglycemic therapies until glycemic targets are reached (1,2), the intensification of therapy in patients with uncontrolled type 2 diabetes (T2D) is often inappropriately delayed. The failure of clinicians to intensify therapy when clinically indicated has been termed “clinical inertia.” A recently published systematic review found that the median time to treatment intensification after an HbA1c measurement above target was longer than 1 year (range 0.3 to >7.2 years) (3). We have previously reported a rather high rate of clinical inertia in patients uncontrolled on metformin monotherapy (4). Treatment was not intensified early (within 6 months of metformin monotherapy failure) in 38%, 31%, and 28% of patients when poor glycemic control was defined as an HbA1c >7% (>53 mmol/mol), >7.5% (>58 mmol/mol), and >8% (>64 mmol/mol), respectively. Using the electronic health record system at Cleveland Clinic (2005–2016), we identified a cohort of 7,389 patients with T2D who had an HbA1c value ≥7% (≥53 mmol/mol) (“index HbA1c”) despite having been on a stable regimen of two oral antihyperglycemic drugs (OADs) for at least 6 months prior to the …

Cost-effectiveness analysis of metformin+dipeptidyl peptidase-4 inhibitors compared to metformin+sulfonylureas for treatment of type 2 diabetes

BackgroundPatients with type 2 diabetes (T2D) typically use several drug treatments during their lifetime. There is a debate about the best second-line therapy after metformin monotherapy failure due to the increasing number of available antidiabetic drugs and the lack of comparative clinical trials of secondary treatment regimens. While prior research compared the cost-effectiveness of two alternative drugs, the literature assessing T2D treatment pathways is scarce. The purpose of this study was to evaluate the long-term cost-effectiveness of dipeptidyl peptidase-4 inhibitors (DPP-4i) compared to sulfonylureas (SU) as second-line therapy in combination with metformin in patients with T2D.MethodsA Markov model was developed with four health states, 1 year cycle, and a 25-year time horizon. Clinical and cost data were collected from previous studies and other readily available secondary data sources. The incremental cost-effectiveness ratio (ICER) was estimated from the US third party payer perspective. Both, costs and outcomes, were discounted at a 3% annual discount rate. One way and probabilistic sensitivity analyses were performed to evaluate the impact of uncertainty on the base-case results.ResultsThe discounted incremental cost of metformin+DPP-4i compared to metformin+SU was $11,849 and the incremental life-years gained were 0.61, resulting in an ICER of $19,420 per life-year gained for patients in the metformin+DPP-4i treatment pathway. The ICER estimated in the probabilistic sensitivity analysis was $19,980 per life-year gained. Sensitivity analyses showed that the results of the study were not sensitive to changes in the parameters used in base-case.ConclusionsThe metformin+DPP-4i treatment pathway was cost-effective compared to metformin+SU as a long-term second-line therapy in the treatment of T2D from the US health care payer perspective. Study findings have the potential to provide clinicians and third party payers valuable evidence for the prescription and utilization of cost-effective second-line therapy after metformin monotherapy failure in the treatment of T2D.