Glycemic Goal Attainment Research Articles

Therapeutic Inertia in the Management of Type 2 Diabetes: A Narrative Review.

Adequate glycemic control is key to prevent morbi-mortality from type 2 diabetes (T2D). Despite the increasing availability of novel, effective, and safe medications for the treatment of T2D, and periodically updated guidelines on its management, the overall rate of glycemic goal attainment remains low (around 50%) and has not improved in the past decade. Therapeutic inertia (TI), defined as the failure to advance or de-intensify medical therapy when appropriate to do so, has been identified as a central contributor to the lack of progress in the rates of HbA1c goal attainment. The time to treatment intensification in patients not meeting glycemic goals has been estimated to be between 1 and 7years from the time HbA1c exceeded 7%, and often, even when an intervention is carried out, it proves insufficient to achieve glycemic goals, which led to the concept of intensification inertia. Therefore, finding strategies to overcome all forms of TI in the management of T2D is a fundamental initiative, likely to have an enormous impact in health outcomes for people with T2D. There are several factors that have been described in the literature leading to TI, including clinician-related, patient-related, and healthcare system-related factors, which are discussed in this review. Likewise, several interventions addressing TI had been tested, most of them proving limited efficacy. Within the most effective interventions, there appear to be two common factors. First, they involve a team-based effort, including nurses, pharmacists, and diabetes educators. Second, they were built upon a framework based on results of qualitative studies conducted in the same context where they were later implemented, as will be discussed in this article. Given the complex nature of TI, it is crucial to use a research method that allows for an in-depth understanding of the phenomenon. Most of the literature on TI is focused on quantitatively describing its consequences; unfortunately, however, not many study groups have undertaken qualitative studies to deeply investigate the drivers of TI in their diverse contexts. This is particularly true in the United States, where there is an abundance of publications exploring the effects of different strategies to overcome TI in type 2 diabetes, but a severe shortage of qualitative studies aiming to truly understand the phenomenon.

Clinical outcomes in high-hypoglycaemia-risk patients with type 2 diabetes switching to insulin glargine 300U/mL versus a first-generation basal insulin analogue in the United States : Results from the DELIVER High Risk real-world study.

AimsTo compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting.MethodsDELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (<7% and <8%), and incidence and event rates of hypoglycaemia (all‐hypoglycaemia and hypoglycaemia associated with an inpatient/emergency department [ED] contact).ResultsHbA1c reductions were similar following switching to Gla‐300 or Gla‐100/IDet (−0.51% vs. −0.53%; p = .67), and patients showed similar attainment of HbA1c goals. Patients in both cohorts had comparable all‐hypoglycaemia incidence and event rates. However, the Gla‐300 switcher cohort had a significantly lower risk of inpatient/ED‐associated hypoglycaemia (adjusted odds ratio: 0.73, 95% confidence interval: 0.60–0.89; p = .002) and experienced significantly fewer inpatient/ED‐associated hypoglycaemic events (0.21 vs. 0.33 events per patient per year; p < .001).ConclusionIn patients with T2D at high risk of hypoglycaemia, switching to Gla‐300 or Gla‐100/IDet achieved similar HbA1c reductions and glycaemic goal attainment, but Gla‐300 switchers had a significantly lower risk of hypoglycaemia associated with an inpatient/ED contact during 12 months after switching.

Real-world Evaluation of glycemic control and hypoglycemic Events among type 2 Diabetes mellitus study (REEDS): a multicentre, cross-sectional study in Thailand

ObjectivePatients with type 2 diabetes mellitus (T2DM) often experience hypoglycaemia and weight gain due to treatment side effects. Sulfonylureas (SU) and the combination of SU and metformin (SU+MET) were the...

1637-P: Role of Initial Combination Therapy on Goal Attainment among Patients with Type 2 Diabetes with High HbA1c

A significant proportion of patients with type 2 diabetes (T2DM) have suboptimal glycemic control which is associated with an increased risk of long-term complications. Clinical guidelines have recommended the use of initial combination therapy, rather than metformin monotherapy, in patients with high HbA1c (≥9%) at diagnosis. However, the adherence to these guideline recommendations and the impact of use of early combination therapy on glycemic goal attainment in the real world is not well known. We conducted a retrospective study using the U.S. Optum Research Database (2010-2015). The study population included T2DM patients aged ≥18 years with a baseline HbA1c of ≥9%. Index date was defined as the first prescription for an antidiabetic agent. Combination therapy was defined as receiving 2 or more antidiabetic classes within 1 month of the index date. During the 2-year follow-up period following the index date, we also compared time to goal attainment (HbA1c of &amp;lt;7%) among patients receiving initial monotherapy vs. initial combination therapy. A total of 13,791 T2DM patients met the inclusion criteria; 34.8% females; mean age: 54 years. Overall 41.4% were initiated on a combination therapy and 58.6% initiated on monotherapy. Patients receiving either treatment were generally similar. Patients receiving combination therapy had a lower mean age (53.0 vs. 54.7), had a higher mean total cholesterol (213 vs. 208 mg/dL) and higher triglyceride (319 vs. 282 mg/dL). The median time to goal attainment was shorter among those on combination therapy vs. monotherapy (318 vs. 372 days). Our study suggests that less than half of newly diagnosed U.S. patients with high HbA1c receive initial combination therapy. Furthermore, those receiving initial combination therapy achieve glycemic goal earlier than patients receiving monotherapy. Disclosure R.M. Klok: Employee; Self; Merck &amp; Co., Inc. Stock/Shareholder; Self; Merck &amp; Co., Inc. T. Gulati: Consultant; Self; Merck &amp; Co., Inc. S. Rajpathak: None. S. Pal: Consultant; Self; Merck &amp; Co., Inc. L. Yang: Employee; Self; Bristol-Myers Squibb Company, Merck &amp; Co., Inc. A. Bandyopadhyay: Consultant; Self; Merck &amp; Co., Inc. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Funding Merck &amp; Co., Inc.

Glycaemic goal attainment and hypoglycaemia outcomes in type 2 diabetes patients initiating insulin glargine 300 units/mL or 100 units/mL: Real-world results from the DELIVER Naïve cohort study.

AimsTo compare HbA1c and hypoglycaemia in insulin‐naïve patients with type 2 diabetes (T2D) who initiated insulin glargine 300 units/mL (Gla‐300) or 100 units/mL (Gla‐100).Materials and methodsThis retrospective cohort study examined electronic medical records of insulin‐naïve adults with T2D who initiated Gla‐300 or Gla‐100 during March 2015 through to December 2016 with active records for ≥12 months before and ≥6 months after initiation, and ≥1 valid HbA1c value during 6‐month baseline and 90–180‐day follow‐up. Outcomes included HbA1c and hypoglycaemia. Cohorts were propensity score‐matched (1:2) on baseline demographic and clinical characteristics. Sensitivity analyses were conducted using broader inclusion criteria.ResultsThe matched cohorts included 1004 Gla‐300 and 2008 Gla‐100 initiators (mean age 60.4 years; 53.2% male). During 6‐month follow‐up, Gla‐300 versus Gla‐100 initiators had a greater mean HbA1c decrease (−1.52 ± 2.08% vs. –1.30 ± 2.12%; P = 0.003) and more patients achieved HbA1c <7% (25.0% vs. 21.5%; P = 0.029) and <8% (55.0% vs. 49.2%; P = 0.002); and HbA1c <7% (21.9% vs. 17.4%; P = 0.003) and <8% (49.1% vs. 41.8%; P < 0.001) without hypoglycaemia. Gla‐300 initiators were similarly or less likely to have any or inpatient/emergency department‐associated hypoglycaemia during 3‐ and 6‐month follow‐up (e.g. any hypoglycaemia to 6 months: 9.7% vs. 12.5%; adjusted odds ratio 0.61; P = 0.057).ConclusionsAmong insulin‐naïve adults with T2D, Gla‐300 was associated with significantly better HbA1c reductions (latest value during 90–180‐day follow‐up) and similar or improved hypoglycaemia outcomes (3‐ and 6‐month follow‐up) than Gla‐100.

Efficacy of iGlarLixi, a fixed-ratio combination of insulin glargine and lixisenatide, in patients with type 2 diabetes stratified as at high or low risk according to HEDIS measurements.

The Healthcare Effectiveness Data and Information Set (HEDIS) measurements assess glycaemic goal attainment in patients with type 2 diabetes, incorporating factors including age and health status. Healthier patients are assigned a glycated haemoglobin (HbA1c) goal of <7% (low-risk [LR]) and individuals aged >65 years or with comorbidities are assigned a goal of <8% (high-risk [HR]). This post-hoc analysis assessed the safety and efficacy of iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide, in 1898 patients from the phase 3 LixiLan-L and LixiLan-O clinical trials, retrospectively classified as LR (n = 1181) or HR (n = 717). iGlarLixi was more effective in reducing HbA1c than comparators in both LR and HR patients across the LixiLan-L trial (change from baseline, 1.1% vs -0.6% for iGlar in both groups; P < 0.001) and the LixiLan-O trial (change from baseline, LR/HR -1.6%/-1.4% vs -1.3%/-1.2% for iGlar and -0.8%/-0.9% for lixisenatide; P < 0.01). iGlarLixi treatment significantly reduced postprandial glucose in both LR and HR patients (P < 0.001). The incidence of hypoglycaemia did not differ between risk categories in any treatment group.

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..

Glycemic Control Outcomes After Canagliflozin Initiation: Observations in a Medicare and Commercial Managed Care Population in Clinical Practice

PurposeAlthough the efficacy of canagliflozin has been well established in clinical trials, research regarding its use and impact on outcomes in clinical practice has been limited by the availability of data on observations up to and beyond 6 months after the initial use of canagliflozin. The purpose of this study was to evaluate changes in glycemic control after the initiation of canagliflozin use in a managed care population. MethodsA retrospective cohort analysis in adults with type 2 diabetes mellitus was conducted using medical and pharmacy claims data and laboratory results from the Humana Research Database. The differences between hemoglobin (Hb) A1c levels pre- and postindex were assessed. Changes from pre- to postindex in the percentages of patients achieving glycemic control (eg, HbA1c <7% or <8%) were evaluated. HbA1c levels were also observed during days 31 to 90, 91 to 180, 181 to 270, and 271 to 360 postindex relative to preindex to assess the durability of HbA1c change over time. Analyses were conducted in the full cohort and in 3 subgroups: (1) HbA1c ≥7% at baseline; (2) age ≥65 years; (3) and Medicare members age ≥65 years and HbA1c ≥7% at baseline. FindingsAmong the 1562 patients meeting the study criteria, the mean HbA1c values pre- and postindex were 8.6% and 7.9%, respectively (P < 0.0001); in the subgroup with HbA1c ≥7% at baseline, these values were 8.9% and 8.0%; in the subgroup aged ≥65 years, 8.5% and 7.9%; and in the subgroup aged ≥65 years with HbA1c ≥7% at baseline, 8.8% and 8.1% (all subgroups, P < 0.001). The percentages of patients meeting glycemic-control thresholds (HbA1c <7%, <8%) were significantly greater at postindex in the full study cohort and in all 3 subgroups (all, P < 0.001). Based on longitudinal HbA1c results in the postindex periods, HbA1c reduction appeared durable across 12 months. ImplicationsThe findings from this study suggest that treatment with canagliflozin is associated with improved glycemic control, as evidenced by HbA1c reduction and glycemic goal attainment. Even though not all patients had valid HbA1c measurements available in each quarter during the follow-up period, the reductions in mean HbA1c appeared durable across the postindex intervals. The observations from this majority Medicare Advantage with Prescription Drug sample and, more specifically, in the subgroups limited to patients aged ≥65 years are particularly informative for payers and providers managing or caring for patients of this age with diabetes.

Glycosylated hemoglobin level and number of oral antidiabetic drugs predict whether or not glycemic target is achieved in insulin-requiring type 2 diabetes

AimsFactors predicting success (glycosylated hemoglobin (A1C)<7%) with insulin therapy in patients with insulin-requiring type 2 diabetes need to be identified. MethodsA retrospective, multi-center, observational study was conducted for outpatients with oral antidiabetic drug (OAD)-treated type 2 diabetes whose A1C levels remained above 7%. Patients were begun on basal insulin between January 2005 and December 2006. Biochemical variables and demographic data were collected before and after 52 weeks of insulin therapy. ResultsA total of 565 patients (age, 60.4±11.9 years; A1C levels, 10.11 ±1.81%; duration of diabetes, 11.5±6.8 years) were studied. By study end, 63 patients (11.2%) had achieved the glycemic goal (A1C<7%). The glycemic goal attainment rate was only 9.1% in patients with A1C>8.8% and who were taking >2 OADs at baseline. The highest rate (32.7%) of successful glycemic control was observed in the group of patients with A1C ≤ 8.8% and who used ≤ 2 OADs at baseline. ConclusionsInsulin-naïve diabetic patients with A1C>8.8%, especially those who are taking >2 OADs, have small chance to achieve good glycemic control with adding only basal insulin therapy.

Determinants of glycaemic control in a practice setting: the role of weight loss and treatment adherence (The DELTA Study).

AimsExamine the association between weight loss and adherence with glycaemic goal attainment in patients with inadequately controlled T2DM.Materials and methodsPatients ≥ 18 years with T2DM from a US integrated health system starting a new class of diabetes medication between 11/1/10 and 4/30/11 (index date) with baseline HbA1c ≥ 7.0% were included in this cohort study. Target HbA1c and weight change were defined at 6-months as HbA1c < 7.0% and ≥ 3% loss in body weight. Patient-reported medication adherence was assessed per the Medication Adherence Reporting Scale. Structural equation modelling was used to describe simultaneous associations between adherence, weight loss and HbA1c goal attainment.ResultsInclusion criteria were met by 477 patients; mean (SD) age 59.1 (11.6) years; 50.9% were female; 30.4% were treatment naïve; baseline HbA1c 8.6% (1.6); weight 102.0 kg (23.0). Most patients (67.9%) reported being adherent to the index diabetes medication. At 6 months mean weight change was −1.3 (5.1) kg (p = 0.39); 28.1% had weight loss of ≥ 3%. Mean HbA1c change was −1.2% (1.8) (p< 0.001); 42.8% attained HbA1c goal. Adherent patients (OR 1.70; p = 0.02) and diabetes therapies that lead to weight loss (metformin, GLP-1) were associated with weight loss ≥ 3% (OR 2.96; p< 0.001). Weight loss (OR 3.60; p < 0.001) and adherence (OR 1.59; p < 0.001) were associated with HbA1c goal attainment.ConclusionsWeight loss ≥ 3% and medication adherence were associated with HbA1c goal attainment in T2DM; weight loss was a stronger predictor of goal attainment than medication adherence in this study population. It is important to consider weight-effect properties, in addition to patient-centric adherence counselling, when prescribing diabetes therapy.

Impact of time to treatment intensification on glycemic goal attainment among patients with type 2 diabetes failing metformin monotherapy

BackgroundPatients with type 2 diabetes on metformin monotherapy frequently require treatment intensification with another anti-hyperglycemic medication over time. Previous studies have indicated that a high proportion of patients with diabetes have a significant delay in the initiation of oral add-on therapy after metformin alone fails to achieve targeted glycemic control. In this study, we evaluated the impact of the timing of treatment intensification with oral add-on drug on glycemic goal attainment among diabetic patients failing metformin monotherapy. Research design and methodsUsing the General Electric (GE) Centricity Electronic Medical Record database (January 2004 through December 2009), we identified 5,870 patients with type 2 diabetes with treatment failure on metformin monotherapy - defined by a glycosylated hemoglobin (HbA1c) of ≥7.5% (index date). This cut-off of ≥7.5% (trigger HbA1c) was chosen rather than that of >7.0% to ensure that selected patients were more likely to be indicated for treatment intensification with add-on drug. Continuous enrollment of one year prior and two years after index date was required to be included in the study. Add-on treatment was defined as prescription of second oral agent from any available therapeutic classes while continuing metformin. Early treatment intensification was defined as initiation of oral add-on therapy within 3months (n=1,012) of index date while late intensification was defined as add-on initiation between 10 and 15months after index date (n=461). The study outcome was defined as glycemic goal attainment (HbA1c<7%), which was evaluated between 18 and 24months after index date. ResultsOur results suggested that at the end of the follow-up period, 47.2% of patients in the early add-on group were at glycemic goal compared to 41.7% in the late add-on group (p=0.039). In a multivariable logistic regression model that accounted for age, gender, trigger HbA1c level, Charlson comorbidity index, anti-hypertensive and anti-hyperlipidemic drug use and history of cardiovascular disease, the adjusted odds ratio (OR) for glycemic goal attainment was 1.36 (95% confidence intervals [CI]: 1.09–1.72) comparing early add-on to late add-on treatment. This association was stronger among patients with higher trigger HbA1c at baseline; ORs of 1.53 (95% CI: 1.08–2.19) for HbA1c ≥8% and 2.63 (95% CI: 1.40–5.27) for HbA1c ≥9%. ConclusionThese results suggest that earlier use of oral add-on drug in treatment regimen helps better achieve glycemic goal attainment in patients with metformin failure. Future studies should evaluate whether earlier treatment intensification is also associated with longer term health outcomes such as risk of microvascular and macrovascular complications.

Improved real‐world glycaemic outcomes with liraglutide versus other incretin‐based therapies in type 2 diabetes

Liraglutide (LIRA) once-daily has provided greater A1C reductions than either exenatide (EXEN) twice-daily or sitagliptin (SITA) once-daily in head-to-head trials. The objective of this analysis is to compare the real-world clinical effectiveness of these agents in the USA. Using the IMS Health (Alexandria, VA, USA) integrated claims database, A1C outcomes in patients aged ≥ 18 years with type 2 diabetes (T2D) who initiated either LIRA, EXEN or SITA (including SITA/metformin) were retrospectively compared. Patients included in the analysis had ≥ 1 prescription for LIRA, EXEN or SITA between January and December 2010 (index period) and persisted with their index treatment regimens for 6 months post-index. Outcomes included changes in A1C from baseline (45 days pre-index through 7 days post-index) to follow-up [6 months post-index (± 45)] and the proportion of patients reaching A1C<7%. Multivariable regression models adjusted for confounding factors (e.g. age, comorbidities, baseline A1C and background antidiabetic therapy). The predicted change in A1C from baseline was greater for LIRA patients compared with both SITA (-1.08 vs. -0.68%; treatment difference 0.40%, p < 0.0001) and EXEN (-1.08 vs. -0.75%; treatment difference 0.32%, p < 0.001). Predicted A1C goal achievement, derived from the multivariate logistic regression model, was higher with LIRA compared with both SITA [64.4% (95% confidence interval, CI: 63.5-65.3) vs. 49.4% (95% CI: 48.5-50.4); p < 0.0001] and EXEN [64.4% (95% CI: 63.5-65.3) vs. 53.6% (95% CI: 52.6-54.6); p < 0.0001]. In clinical practice, LIRA was associated with significantly greater reductions in A1C and improved glycaemic goal attainment compared with either EXEN or SITA among adult patients with T2D.

Comparative Real World Effectiveness of Liraglutide versus Sitagliptin in Patients with Type 2 Diabetes as an Add-On to Metformin Monotherapy in the United States

Objective: Limited real-world evidence is available on the effectiveness of liraglutide compared with sitagliptin as an add-on therapy to metformin in clinical practice for adult patients with Type 2 diabetes mellitus (T2DM). The purpose of this study was to compare clinical outcomes 6 months after initiating treatment with liraglutide or sitagliptin for patients uncontrolled on metformin monotherapy in the United States (US). Methods: We used the General Electric Centricity electronic medical records database to analyze the effectiveness of liraglutide and sitagliptin in adult (≥18 years) patients with T2DM who started either drug between January 1, 2010 and January 31, 2013 (index period) as an add-on to metformin monotherapy. Changes in A1C, body weight, and the proportion of patients reaching ADA A1C target of <7.0% 6 months after starting treatment with liraglutide or sitagliptin, adjusted for differences in demographic and baseline clinical characteristics, were evaluated. Results: 395 patients treated with liraglutide (mean age: 52.9 years, female: 57.5%) and 1,896 patients treated with sitagliptin (mean age: 58.0 years, female: 51.1%) were identified during the index period. After adjusting for baseline factors, patients treated with liraglutide experienced greater reductions in A1C (-1.18% vs. -0.94%, p<0.001) and body weight (-3.0 kg vs. -1.6 kg [6.6 lbs vs. -3.4 lbs], p<0.001) at 6 months from baseline than patients treated with sitagliptin. Significantly more patients treated with liraglutide met the A1C <7.0% target after 6 months follow-up (49.4% vs. 40.0%, p=0.001). Conclusions: As in clinical trials, this real-world study found that among adult patients with T2DM uncontrolled on metformin monotherapy liraglutide was associated with significantly greater reductions in A1C and body weight and improved glycemic goal attainment compared to sitagliptin.

Enhanced glycemic control with combination therapy for type 2 diabetes in primary care.

Type 2 diabetes mellitus is an increasingly common medical problem for primary care clinicians to address. Treatment of diabetes has evolved from simple replacement of insulin (directly or through insulin secretagogs) through capture of mechanisms such as insulin sensitizers, alpha-glucosidase inhibitors, and incretins. Only very recently has recognition of the critical role of the gastrointestinal system as a major culprit in glucose dysregulation been established. Since glycated hemoglobin A1c reductions provide meaningful risk reduction as well as improved quality of life, it is worthwhile to explore evolving paths for more efficient use of the currently available pharmacotherapies. Because diabetes is a progressive disease, even transiently successful treatment will likely require augmentation as the disorder progresses. Pharmacotherapies with complementary mechanisms of action will be necessary to achieve glycemic goals. Hence, clinicians need to be well informed about the various noninsulin alternatives that have been shown to be successful in glycemic goal attainment. This article reviews the benefits of glucose control, the current status of diabetes control, pertinent pathophysiology, available pharmacological classes for combination, limitations of current therapies, and suggestions for appropriate combination therapies, including specific suggestions for thresholds at which different strategies might be most effectively utilized by primary care clinicians.