Noninsulin Antihyperglycemic Agents Research Articles

6779 The Diversity of Immune Checkpoint Inhibitor Associated Diabetes

Abstract Disclosure: V.A. Mendpara: None. M. Lansang: None. M. Caromori: None. L. Kennedy: None. K. Zhou: None. Immune checkpoint inhibitor (ICI) treatment has become a first-line therapy for a variety of cancers, including use of nivolumab (a programmed death 1 [PD-1] inhibitor) for metastatic melanoma. Though able to prolong survival, ICIs cause immune-related adverse events (irAE) through down-regulation of immune control pathways. One irAE is diabetes mellitus (DM), referred to as ICI-induced DM. Despite its low incidence (2%), ICI-induced DM carries with it high morbidity, with need for hospitalization in up to 25% of patients, and burden as patients are typically committed to multiple daily insulin injections (MDII). Here we report diverse presentations of four patients treated with ICI for metastatic melanoma who developed ICI-induced DM. The median age at DM presentation was 60.5 years (range 59-78 years). All patients received nivolumab and one patient was also treated with ipilimumab (a cytotoxic T-lymphocyte-associated antigen 4 inhibitor). The median time from start of ICI to development of ICI-induced DM was 32.5 wks, ranging from 27-46 wks. Three of the 4 patients previously developed hypothyroidism at median of 15 wks from starting ICI. Two patients presented in DKA and the other 2 with severe hyperglycemia (glucose >300 mg/dL). Median HbA1c was 7.05% (range 6.4%-7.4%) at presentation. GAD Ab was negative in 3 of 4 patients, including one who had DKA. C-peptide was undetectable (<0.2 ng/mL) in the 2 patients with DKA, 0.4 ng/mL in one other patient, and not measured in the fourth. All patients were immediately started on MDII. However, the two patients without DKA on presentation were eventually initiated on non-insulin agents. One of them was started on a DPP-4 inhibitor and discontinued fast-acting insulin, and the other started a GLP-1 receptor agonist and reduced their fast-acting insulin requirement. The heterogeneity of DM presentation and its clinical course reported here highlights a few important points. The first is that the onset of ICI-induced DM is often much later than that of the most common endocrine irAE, hypothyroidism, which has an onset around 10 weeks in average. Second, DM often presents as severe hyperglycemia incidentally detected on blood work. GAD Ab positivity is relatively less common, suggesting a different underlying etiology than classic type 1 DM. Onset of severe hyperglycemia can occur over many weeks (as indicated by higher HbA1c), making it important to monitor for hyperglycemia in those with no previous history of prediabetes or DM. Finally, it may be possible to use a combination of non-insulin antihyperglycemic agents to provide better glycemic management. No widely validated strategies for the surveillance of irAEs are currently available, and a better understanding in the propensity of patients to develop irAEs is clearly required. Importantly, optimal management of irAEs relies on early recognition and frequently demands a multidisciplinary approach. Presentation: 6/2/2024

Basal Insulin Initiation in Adults With Type 2 Diabetes Mellitus: A Retrospective Cohort Study Using Administrative Health Data in Alberta, Canada

ObjectivesPharmacologic treatment of type 2 diabetes mellitus (T2DM) follows a stepwise approach. Typically, metformin monotherapy is first-line treatment, followed by other noninsulin antihyperglycemic agents (NIAHAs) or progression to insulin if glycated hemoglobin (A1C) targets are not achieved. We aimed to describe real-world patterns of basal insulin initiation in people with T2DM and A1C not at target despite treatment with at least 2 NIAHAs. MethodsA retrospective cohort study was conducted using administrative health data from Alberta, Canada, among adults with T2DM, indexed on the first test with 7.0% < A1C < 9.5% (April 1, 2011, to March 31, 2019), with at least 2 previous NIAHAs but no insulin. Kaplan–Meier (KM) methodology was used to analyze time to basal insulin initiation, with stratification by index A1C. Annual patient status was categorized into 5 groups: basal insulin initiation, death, NIAHA intensification, no change in therapy (subgroups of A1C <7.1% and A1C ≥7.1% [clinical inertia]), or discontinuance. ResultsThe cohort included 14,083 individuals. The KM cumulative probability of initiating basal insulin was 7.7% (95% confidence interval [CI] 7.3% to 8.2%) at 1 year, increasing to 43.1% (95% CI 42.1% to 44.1%) at 8 years of follow-up. Higher A1C levels were associated with greater proportions of basal insulin initiation. By year 8, proportions with NIAHA intensification and clinical inertia were 12.1% and 19.3%, respectively, relative to year 7. ConclusionsDespite current clinical practice guidelines recommending achieving A1C targets within 6 months, less than half of the individuals with T2DM and clear indications for basal insulin initiated treatment within 8 years. Efforts to reduce delays in basal insulin initiation are needed.

Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database

BackgroundMetformin is recommended as a first-line drug in the guidelines of the treatment for type 2 diabetes mellitus. However, high-quality evidence from clinical trials directly comparing the degree of hypoglycemic effect of combination therapy of metformin and a hypoglycemic agent with a different mechanism of action with that of monotherapy of a hypoglycemic drug is lacking. We aimed to examine whether combination therapy of hypoglycemic agents with metformin showed antagonism, addition, or synergism compared to monotherapy with hypoglycemic agents other than metformin regarding hemoglobin A1c levels.MethodsThis retrospective cohort study used a medical information database in Japan. Non-insulin anti-hyperglycemic agents with different mechanisms of action were classified into eight drug classes. A monotherapy cohort and a combination therapy added to the metformin cohort were defined. The change in hemoglobin A1c levels was evaluated to compare the treatment effect between the cohorts.ResultsA total of 13,359 patients with type 2 diabetes mellitus in the monotherapy cohort and 1,064 in the metformin combination therapy cohort were identified. A comparison of the change from baseline HbA1c level by drug class between the two cohorts showed a similar trend. Among those treated with dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter-2 inhibitor, no clinically significant difference was observed between the two cohorts (0.00% and -0.07% for unadjusted, 0.15% and -0.03% for propensity score matching-adjusted, and 0.09% and -0.01% for inverse probability treatment weighting-adjusted analysis).ConclusionsAccording to the results of this study, the effect of dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor added to metformin seems to be additive with respect to the reduction in hemoglobin A1c.

Adverse Birth and Child Outcomes in Children Fathered by Men Treated with Antidiabetics Prior to Conception: A Nationwide Cohort Study.

The safety of fathers' use of antidiabetic drugs in terms of child outcomes is an important clinical question. We aimed to assess the risk of adverse birth and early childhood outcomes after fathers' use of antidiabetics prior to conception. A nationwide cohort study based on Danish health registries. The study comprised all live born singleton children in Denmark (1997 through 2018). Children were categorized according to fathers' filled prescriptions for antidiabetic drugs three months prior to conception. Exposed cohorts: children born after paternal use of insulin or non-insulin anti-hyperglycemic agents. The unexposed constituted children born by fathers not treated with antidiabetics prior to conception. We examined adverse birth outcomes (preterm birth, small for gestational age (SGA)), and adverse childhood outcomes in the first year of life (major congenital malformations (MCMs), and infections diagnosed at a hospital). A total of 1,318,684 children were included. In all, 5527 children were born after paternal use of insulin, 2121 after use of non-insulin anti-hyperglycemic agents, and 1,311,036 were unexposed. After fathers' use of insulin we did not find increased risk of adverse outcomes. After fathers' use of metformin, the adjusted OR of MCMs was 1.40 (95% CI 1.11-1.76). After fathers' use of sulfonylureas, the adjusted OR of SGA was 1.80 (95% CI 1.11-2.93), and for child gastrointestinal infections the adjusted HR was 1.76 (95% CI 1.04-2.99). Fathers' use of insulin was reassuring. Metformin and sulfonylureas were associated with selected adverse outcomes. Our findings suggest an additional 14 MCMs per 1000 fathers exposed to metformin prior to conception. As there is no meaningful supporting biological rationale, these findings should be confirmed in a different population prior to clinical consequences being drawn.

Effects of a Digital Patient Empowerment and Communication Tool on Metabolic Control in People With Type 2 Diabetes: The DeMpower Multicenter Ambispective Study.

BackgroundDiabetes is a major health care problem, reaching epidemic numbers worldwide. Reducing hemoglobin A1c (HbA1c) levels to recommended targets is associated with a marked decrease in the risk of type 2 diabetes mellitus (T2DM)–related complications. The implementation of new technologies, particularly telemedicine, may be helpful to facilitate self-care and empower people with T2DM, leading to improved metabolic control of the disease.ObjectiveThis study aimed to analyze the effect of a home digital patient empowerment and communication tool (DeMpower App) on metabolic control in people with inadequately controlled T2DM.MethodsThe DeMpower study was multicenter with a retrospective (observational: 52 weeks of follow-up) and prospective (interventional: 52 weeks of follow-up) design that included people with T2DM, aged ≥18 and ≤80 years, with HbA1c levels ≥7.5% to ≤9.5%, receiving treatment with noninsulin antihyperglycemic agents, and able to use a smartphone app. Individuals were randomly assigned (2:1) to the DeMpower app–empowered group or control group. We describe the effect of empowerment on the proportion of patients achieving the study glycemic target, defined as HbA1c≤7.5% with a ≥0.5% reduction in HbA1c at week 24.ResultsDue to the COVID-19 pandemic, the study was stopped prematurely, and 50 patients (33 in the DeMpower app–empowered group and 17 in the control group) were analyzed. There was a trend toward a higher proportion of patients achieving the study glycemic target (46% vs 18%; P=.07) in the DeMpower app group that was statistically significant when the target was HbA1c≤7.5% (64% vs 24%; P=.02) or HbA1c≤8% (85% vs 53%; P=.02). The mean HbA1c was significantly reduced at week 24 (−0.81, SD 0.89 vs −0.15, SD 1.03; P=.03); trends for improvement in other cardiovascular risk factors, medication adherence, and satisfaction were observed.ConclusionsThe results suggest that patient empowerment through home digital tools has a potential effect on metabolic control, which might be even more relevant during the COVID-19 pandemic and in a digital health scenario.

Association between first-line monotherapy with metformin and the risk of atrial fibrillation (AMRAF) in patients with type 2 diabetes

BackgroundType 2 diabetes (T2D) has a strong association with atrial fibrillation (AF) which increases risk of thromboembolic events, heart failure, and frequent hospitalizations. Metformin is the first-line medication for T2D with proposed anti-inflammatory, pro-metabolic, and cardio-protective benefits. Our objective was to investigate if initial therapy with metformin is associated with reduced incidence of AF in comparison to other non-insulin anti-hyperglycemic agents in patients with newly diagnosed T2D. MethodsThis retrospective cohort analysis included adults with a new diagnosis of T2D who were started on monotherapy (except insulin) between 2007 and 2017, without prior anti-hyperglycemic agent use, history of arrhythmias, or estimated GFR (eGFR) ≤ 30 ml/min. A multivariate analysis was performed using a fine-gray regression competing risk analysis to control for confounding variables after which pooled hazard ratios and 95 % confidence intervals were reported. Patients were followed until the end of study date, development of AF, addition of more anti-hyperglycemic agents, or death, whichever occurred first. ResultsAmong 4584 metformin initiators compared to 1080 non-metformin monotherapy initiators, 10-year cumulative incidence of AF in metformin group was 5.2 % as compared to 8.1 % with other agents which was not statistically significant. Competing risk analysis did not demonstrate reduced rates of AF with metformin use (HR 0.92, 95 % CI 0.69 to 1.21; P = 0.55). Increased age and the presence of congestive heart failure were associated with significantly higher risk of AF in both groups (HR: 1.29, 95 % CI: 1.21 to 1.37; P ≤ 0.001; HR: 2.73, 95 % CI: 1.62 to 4.61; P ≤ 0.001, respectively). ConclusionInitiation of metformin as a first line monotherapy for T2D, when compared to other non-insulin monotherapies, was not associated with decreased risk of developing AF in this retrospective observational study.

Abstract 10401: Uptake and Predictors of SGLT2i in Patients with Type 2 Diabetes and Cardiovascular Disease

Introduction: While sodium glucose cotransporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in type 2 diabetes (T2D) and cardiovascular disease (CVD), their uptake in clinical practice in this population is unclear. Therefore, we evaluated trends in SGLT2i use and identified predictors of use in patients with concomitant T2D and CVD. Methods: We conducted an observational study using population-based health data in Ontario, Canada from 4/2016-3/2020 of patients ≥65 years old with a first diagnosis of T2D plus CVD. In each yearly cohort, we estimated the prevalent use of SGLT2i (≥1 prescription) within 1 year, including by demographic and comorbidity subgroups. In the overall cohort, we used multivariable logistic regression models to identify factors associated with SGLT2i use. Results: We identified 208,303 patients with T2D and CVD [median age 74.0 years (IQR 68.0-80.0); 63.5% male]. The proportion of patients dispensed an SGLT2i increased over time, from 7.0% in 2016 to 20.1% in 2019. In 2019, use in those ≥75 years was 50% lower than those &lt;75 years (12.9% vs. 28.3%;p&lt;.0001), and use in those without chronic kidney disease (CKD) was 50% higher than those with CKD (22.0% vs. 15.0%;p&lt;.0001); although SGLT2i use increased in all groups over time. Independent factors associated with increased odds of SGLT2i use were HbA1c ≥8 vs. &lt;7 (OR 3.33, 95%CI:3.22-3.46), use of 2+ non-insulin antihyperglycemic agents (OR 2.63, 95%CI:2.56-2.71), and an endocrinologist visit in prior year (OR 1.50, 95%CI:1.45-1.55). Those &gt;75 years (OR 0.39, 95%CI:0.38-0.40), with high frailty score (OR 0.38, 95%CI:0.35-0.42), or serum creatinine 1.4-2mg/dL vs. &lt;1.4 (OR 0.55, 95%CI:0.52-0.57) were less likely to use SGLT2i. Conclusions: In a real-world population of T2D and CVD, only 1 in 5 patients used an SGLT2i, although use increased over time. Markers of worse diabetes control were associated with increased SGLT2i use, while markers of more comorbidity were associated with less use.

Variability of Clinical Practice Management of Type 1 and Type 2 Diabetes During Surgery Across Canada

ObjectiveAs part of a larger project to develop quality standards in perioperative diabetes management, the goal of this project was to assess self-reported management of surgical patients with diabetes across healthcare institutions and specialties in Canada. MethodsCurrent practice of perioperative management of patients with diabetes was assessed using multiple-choice questions based on commonly encountered clinical scenarios involving patients with type 1 and type 2 diabetes. The survey was sent to a broad stakeholder group of individuals involved in perioperative medicine in academic and community settings across Canada. ResultsResponses to clinical case scenarios demonstrated more consistent approaches for patients with type 1 diabetes undergoing cardiac surgery, possibly reflecting more robust evidence. There was more variability in the management of noninsulin antihyperglycemic agents and hyperglycemia in patients with type 2 diabetes undergoing noncardiac surgery. ConclusionsGiven the variability in clinical practice, standards and clinical tools are required for perioperative and periprocedural glycemic management in Canada to inform practice, improve the experience and outcomes for people with diabetes and provide a foundation for quality improvement initiatives and benchmarking.

Adjunct Antihyperglycemic Agents in Overweight and Obese Adults With Type 1 Diabetes.

People with type 1 diabetes often have suboptimal glycemic control. The gold standard of treatment is basal-bolus insulin or subcutaneous insulin infusion via insulin pump. Although insulin therapy improves glycemic control, weight gain and hypoglycemia often limit achievement of hemoglobin A1C (A1C) goals. The number of people with type 1 diabetes who are overweight or obese is increasing, and there are many similarities between what was historically called type 1 and type 2 diabetes. Therefore, there is rationale for using antihyperglycemic agents that target other pathophysiological abnormalities to facilitate weight loss and improve glycemic control. We performed a MEDLINE search from 1975 through October 2018 to identify articles that studied noninsulin agents in adults with type 1 diabetes and body mass index (BMI) ≥25 kg/m2. Identified articles were included if the study duration was ≥4 weeks, included ≥20 patients, and set mean baseline BMI ⩾25kg/m2. This review summarizes 32 clinical trials. Amylin mimetics, sodium-glucose-like transporter-2 inhibitors, and glucagon-like-peptide-1 receptor agonists demonstrate the greatest improvements in body weight and A1C. The most common adverse effects are hypoglycemia and ketosis. Relevance to Patient Care and Clinical Practice: Patients with type 1 diabetes may have interest in starting noninsulin agents. Clinicians need to be knowledgeable in the efficacy and adverse effect profile of these agents, specifically in people with type 1 diabetes. Adding noninsulin antihyperglycemic agents may benefit select overweight or obese adults with type 1 diabetes. These agents are off-label, and if used, close monitoring is essential.

Glycated Hemoglobin Level Goal Achievement in Adults With Type 2 Diabetes in Canada: Still Room for Improvement.

To describe the clinical histories and management of adults with type 2 diabetes who were not reaching their target glycated hemoglobin (A1C) levels and to identify barriers to achieving therapeutic goals. Practice assessment surveys and practice audits were completed by 88 primary care physicians (PCPs) in the Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program and by 56 diabetes specialists in the Diabetes Mellitus IMproving PAtient Care in our communiTies (DM-IMPACT) program. The DM-ACTION audit analyzed data from 1,173 adults with A1C levels ≥7.3% who were not prescribed insulin; the DM-IMPACT audit included 135 individuals with similar characteristics. Most PCPs (92%) and specialists (88%) stated that they typically recommend A1C levels of ≤7.0%; more than 90% indicated that they adjusted antihyperglycemic therapy within 3months if suboptimal A1C targets endured. Among the DM-ACTION patients, the median A1C level was 7.8%; the median time between the last 2 A1C tests was 5months; 58% were taking ≤2 noninsulin antihyperglycemic agents; and adjustment of glucose-lowering therapy was noted for only 56%. The corresponding values for the DM-IMPACT patients were 8.0%, 4months, 43% and 68%, respectively. PCPs and specialists attributed patients' factors and patients' adherence as primary causes of poor achievement of guideline-recommended targets. PCPs perceived patients' factors as the predominant barrier to optimizing care, but the specialists believed that therapeutic inertia stems from a wide range and a varied combination of patient-centric factors. Type 2 diabetes remains a health-care challenge in Canada and globally. Primary care physicians and specialists attributed patients' factors as principal obstacles to optimal diabetes management. However, physician-associated therapeutic inertia may also be an important barrier to unmet therapeutic goals.

On Time—An Innovative Online Discussion Tool to Overcome Barriers to Insulin Initiation

The On Time education program is an innovative, online point-of-care tool designed to uncover and address barriers to insulin initiation, and to facilitate timely insulin initiation, when appropriate, in insulin-naïve individuals with type 2 diabetes (T2D). A total of 195 health care professionals (HCPs) completed online profiles of 1025 insulin-naïve individuals with T2D currently treated with non-insulin antihyperglycemic agents (NIAHAs) and with a glycated hemoglobin (A1C) above the Diabetes Canada target (for most individuals ≤7%). After having completed the discussion tool and questionnaires, participating HCPs were asked to evaluate the program, tool, and questionnaires. Mean age of participants was 61.2 years; 55% were male; mean duration of diabetes was 10.5 years. For the majority of participants (70%) the recommended A1C target was ≤7.0%. On average, participants were prescribed 2.6 NIAHAs, mainly metformin and dipeptidyl peptidase-4 inhibitors. Prior to using the On Time discussion tool, only 23% of individuals with diabetes were judged as likely (16%) or extremely likely (7%) willing to initiate insulin. The leading barriers to initiating insulin were apprehension toward needles/injections (59%), belief that insulin was complicated (56%), and psychological insulin resistance (45%). After using the On Time discussion tool, participants’ perceived willingness to initiate insulin increased (likely: 34%, extremely likely: 28%). Initiation of insulin was planned in 77% of participating individuals. The evaluation questionnaire was completed by 149 HCPs (76.4%), and showed that the discussion tool was perceived to help HCPs address insulin-related barriers (82%), positively impacted their practice (79%), and improved their approach when discussing insulin initiation with individuals with diabetes (76%). Identifying the barriers to initiating insulin and providing educational interventions to address them may help to improve insulin acceptance. Disclosure J. Gilbert: Other Relationship; Self; AstraZeneca, Boehringer Ingelheim GmbH, Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Janssen Pharmaceuticals, Inc., Sanofi. G. MacNeill: Consultant; Self; Becton, Dickinson and Company. Advisory Panel; Self; Janssen Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk Inc.. Consultant; Self; Sanofi. E.M. Cooke: Other Relationship; Self; Abbott. Speaker's Bureau; Self; Becton, Dickinson and Company, LifeScan Canada. Other Relationship; Self; LifeScan Canada. Speaker's Bureau; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Other Relationship; Self; Sanofi, mdBriefCase Group.P. Filteau: None. M. Vallis: Speaker's Bureau; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; AbbVie Inc.. Advisory Panel; Self; Valeant Pharmaceuticals International, Inc.. Speaker's Bureau; Self; Merck &amp; Co., Inc.. Advisory Panel; Self; Sanofi. Speaker's Bureau; Self; Sanofi. M. Groleau: Employee; Self; Sanofi. P. Javadi: Employee; Self; Sanofi. C. Lebovics: Employee; Self; Sanofi.

Characteristics of insulin-Na\xefve people with type 2 diabetes who successfully respond to insulin glargine U100 after 24\xa0weeks of treatment: a meta-analysis of individual participant data from 3 randomized clinical trials

BackgroundTo identify baseline/clinical characteristics associated with clinically meaningful responses to insulin glargine 100 U/mL (IGlar) in insulin-naive people with type 2 diabetes mellitus (T2DM).MethodsIndividual participant data were pooled from 3 randomized trials to compare baseline characteristics and clinical outcomes associated with 24-week response to IGlar in combination with non-insulin antihyperglycemic agents in participants with T2DM. Responders were defined as achieving endpoint HbA1c target < 53 mmol/mol (< 7%) and/or ≥ 11 mmol/mol (≥ 1%) HbA1c reduction from baseline.ResultsDifferences in baseline characteristics for responders versus nonresponders were higher HbA1c (99 vs 91 mmol/mol [9.1 vs 8.3%]; P < 0.001), higher fasting blood glucose (FBG; 10.4 vs 8.8 mmol/L [187 vs 159 mg/dL; P < 0.001), and fewer participants (94% vs 98%; P = 0.006) taking oral medications targeting postprandial blood glucose (BG). Most participants (80%) achieved one or both components of composite endpoint. 12-week response was a strong predictor of subsequent 24-week response (sensitivity, 85.9%; predictive positive value, 91.4%). At both 12 and 24 weeks, < 40% of responders and nonresponders reached target FBG ≤ 5.6 mmol/L (≤ 100 mg/dL). Responders at 24 weeks had higher incidence of hypoglycemia (total, 82.5% vs 70.4%; P < 0.001; nocturnal, 60.3% vs 50.5%; P = 0.002; documented symptomatic, 65.8% vs 55.6%; P < 0.001) than nonresponders.ConclusionsBaseline characteristics associated with response were identified. The strong predictability of 12-week response suggests that the magnitude of early HbA1c reduction should be considered when assessing response to IGlar. More aggressive IGlar titration may be reasonable for nonresponders and responders who have not reached FBG and HbA1c targets, taking into account other BG timepoints.

Physical Activity and Diabetes.

Physical Activity and Diabetes.

Type 2 Diabetes (T2D) Management in Primary Care: Still Room for Improvement

The Diabetes Mellitus Assessment of Clinical managemenT In ONtario (DM-ACTION) program sought insights into the management of adults with T2D not at guideline recommended A1C. 88 primary care physicians completed practice surveys, 90% of whom saw >10 persons with diabetes/week. Between 9/2016 and 5/2017, data from 1165 adults with T2D, recent A1C ≥7.3%, and managed with lifestyle strategies ± non-insulin antihyperglycemic agents (AHAs) were analyzed. The cohort (60% men) had a median (interquartile range) age of 61 (53–68) years, T2D for 8 (5–12) years, A1C 7.8 (7.4–8.5)%, BP 126/78 (120–132/70–80) mmHg and LDL-C 1.9 (1.4–2.6) mmol/L. BP <130/80 mmHg was documented for 44%; LDL-C≤2.0 mmol/L for 57%; 28% met both targets. Most (86%) had a BMI ≥25.0 kg/m2; 66% had hypertension, 69% dyslipidemia and 10% had an eGFR<60 mL/min/1.73m2. Most (83%) were using ≤3 AHAs. Although 94% of the physicians reported typically initiating/adding an AHA within 3 months for unmet A1C goals, AHA uptitration/initiation/switching was only recorded for 56% of the patient cohort. Furthermore, the last two A1C measurements were 5 (3–7) months apart; only 21% had a≥0.5% A1C decrease while 34% had a≥0.5% increase. Suboptimal glycemic control was most commonly attributed to non-adherence.

Current therapeutic approaches in the management of hyperglycemia in chronic renal disease.

Diabetes mellitus (DM) and chronic kidney disease (CKD) are intricately intertwined. DM is the most common cause of CKD. Adequate control of DM is necessary for prevention of progression of CKD, while careful management of the metabolic abnormalities in CKD will assist in achieving better control of DM. Two of the key organs involved in glucose production are the kidney and the liver. Furthermore, the kidney also plays a role in glucose filtration and reabsorption. In CKD, monitoring of glycemic control using traditional methods such as Hemoglobin A1c (Hba1c) must be done with caution secondary to associated hematological abnormalities in CKD. With regard to medication management in the care of patients with DM, CKD has significant effects. For example, the dosages of oral and non-insulin anti-hyperglycemic agents often need to be modified according to renal function. Insulin metabolism is altered in CKD, and a reduction in insulin dose is almost always needed. Dialysis also affects various aspects of glucose homeostasis, necessitating appropriate changes in therapy. Due to the aforementioned factors glycemic management in patients with DM and CKD can be quiet challenging.

Proximal Predictors of Long-Term Discontinuance with Noninsulin Antihyperglycemic Agents.

Noninsulin antihyperglycemic agents (NAAs) are the mainstay of treatment for type 2 diabetes, yet persistence in NAA use is suboptimal in many diabetes patients. Most of the research on NAA discontinuance has focused on sociodemographic characteristics and general health status, but such factors are inherently limited in explaining dynamic events such as discontinuance. To assess the relative importance of static and proximal dynamic factors in explaining long-term NAA discontinuance among Medicare beneficiaries with diabetes. Two sets of probability models were estimated to predict NAA discontinuance as a function of static variables (age, sex, race, original reason for Medicare entitlement, low-income subsidy and dual Medicare/Medicaid eligibility status, and disease burden) and 21 dynamic factors capturing month-by-month changes in drug use, health status, and use of medical services leading up to discontinuance (defined as month 0) and the previous 4 months (designated months -1 to -4) among 71,619 patients with diabetes enrolled in Medicare Part D plans in 2006-2008. Static variables explained just 1.2% of the variance in probability of NAA discontinuance compared with 14% for all variables combined. Key time-related predictors of NAA discontinuance included discontinuation with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and statins, hypoglycemia, NAA usage gaps, insulin use, and discharge from hospitals and skilled nursing facilities (SNFs). The strongest significant predictors (P < 0.05) of NAA discontinuance were discontinuation with statins and ACEIs/ARBs in month 0 (predicted probabilities of 37% and 34%, respectively). Other variables that significantly increased the probability of NAA discontinuance by 10% or more were hypoglycemia in month 0 (14%) and month -1 (17%), discontinuance with ACEIs/ARBs in months -1 (15%) and -2 (10%), discontinuance with statins in month -1 (13%), and insulin use in month 0 (12%). Experiencing a previous gap in NAA therapy was associated with higher likelihood of discontinuance if the gap occurred in month -2 (10%) or month -4 (6%), but a gap in therapy in month -1 actually reduced the likelihood of discontinuance by 13%. Discharge from a hospital or SNF was consistently associated with higher probabilities of NAA discontinuance ranging between 4% and 10%, with higher probabilities occurring closer to month 0. A cascade of dynamic changes preceding discontinuance with NAA therapy among Medicare Part D enrollees with diabetes was observed between 2006 and 2008. Understanding that lack of persistence in drug use is a dynamic rather than a static phenomenon opens up new avenues for investigating and ultimately improving adherence behavior in the elderly. This study was funded by Merck & Co. Huang and Raipathak are employees of Merck & Co. Brandt reports consultancy and speaker fees from Catapult, Omnicare, RAND, HRSA, CMS, and AGS Beers Criteria. Loh is currently employed at Touro College of Pharmacy. All other authors have no relevant potential conflicts of interest to disclose. Study concept and design were primarily contributed by Stuart, Quinn, and Brandt, along with Shen, Roberto, Hendrick, Huang, and Rajpathak. Shen, Loh, Hendrick, and Kim collected the data, and data interpretation was performed primarily by Stuart, Shen, and Roberto, assisted by Quinn, Brandt, Hendrick, Huang, and Rajpathak. The manuscript was written primarily by Stuart, with assistance from the other authors, and revised by Huang, Rajpathak, and Stuart, with assistance from the other authors.

Cross-National Variation in Glycemic Control and Diabetes-Related Distress Among East Asian Patients Using Insulin: Results from the MOSAIc Study.

IntroductionGuidelines recommend insulin progression for patients with type 2 diabetes (T2D) with inadequate glycemic control. The Multinational Observational Study Assessing Insulin use (MOSAIc [ClinicalTrials.gov identifier, NCT01400971]) study is a 2-year observational study, investigating factors that influence insulin progression in T2D patients. In this first of two reports, we describe baseline clinical and psychosocial characteristics of Chinese, Japanese, and South Korean patients who participated in MOSAIc. Insulin treatment, factors affecting progression, and outcomes will be reported separately.MethodsPatients with T2D using insulin for ≥3 months were eligible. Baseline demographic, clinical, and psychosocial data were collected from patients. Quality of life instruments, including the Diabetes Distress Scale (DDS), were used to assess patient’s concerns about disease management, support, and emotional burden. The association between the DDS and the selected covariates was also assessed.ResultsA total of 373 patients in China, 157 in Japan, and 141 in South Korea were enrolled from July 2011 to July 2013. Mean ± standard deviation duration (years) of T2D differed across countries (China 11.4 ± 7.5; Japan 13.8 ± 8.7; South Korea 15.7 ± 8.8; P < 0.0001). Japanese patients used more noninsulin anti-hyperglycemic agents than did Chinese or South Korean patients (P < 0.0001). Exclusive use of basal insulin was most common in Japan and South Korea compared with China, whereas approximately 66.8% of Chinese patients used mixed insulin. Covariates associated with the DDS were younger age [P = 0.044 (Japan)], higher incidence of monthly hypoglycemia [P = 0.036 [China]; P = 0.021 (South Korea)], and male gender [P = 0.037 (South Korea)].ConclusionsThere were significant differences amongst East Asian patients with T2D treated with insulin, including in quality of life scores. Results from the MOSAIc longitudinal analyses will further investigate trends of insulin intensification and barriers to insulin progression.FundingEli Lilly and Company.

Abstracts from ATTD 2016 9th International Conference on Advanced Technologies & Treatments for Diabetes Milan, Italy-February 3-6, 2016.

Abstracts from ATTD 2016 9th International Conference on Advanced Technologies & Treatments for Diabetes Milan, Italy-February 3-6, 2016.

The effect of a dual combination of noninsulin antidiabetic drugs on lipids: a systematic review and network meta-analysis

Objective:As an ever widening array of anti-hyperglycemic agents are now available, the effect of these drugs on lipids is increasingly complex and controversial. The present meta-analysis was designed to clarify the effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids in type 2 diabetes.Methods:Randomized controlled trials comparing different dual combinations of antidiabetic drugs were identified by searching PubMed, Cochrane Library, and Embase. Study selection, data abstraction and quality assessment were carried out by two reviewers independently. Change in low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride and total cholesterol were pooled by both traditional meta-analysis and network meta-analysis.Results:Eighteen studies with a total of 10,222 patients were included. Network meta-analysis suggested that metformin + dipeptidyl peptidase-4 inhibitors (DPP-4) (LDL cholesterol: −0.19 mmol/L; HDL cholesterol: 0.06 mmol/L; triglycerides: −0.73 mmol/L; total cholesterol: −0.4 mmol/L) and metformin + glucagon-like peptide-1 (GLP-1) agonist (LDL cholesterol: −0.3 mmol/L; HDL cholesterol: 0.06 mmol/L; triglycerides: −0.64 mmol/L; total cholesterol: −0.5 mmol/L) were associated with relatively larger beneficial effects on the lipid profile among all combinations. Compared with metformin + thiazolidinedione, metformin + GLP-1 agonist (mean difference: −0.38; 95% confidence interval [CI]: −0.66 to −0.10) significantly decreased LDL cholesterol. Metformin + thiazolidinedione showed a larger increase than metformin + sulfonylurea in HDL cholesterol (mean difference: 0.1; 95% CI: 0.01 to 0.21).Conclusions:The effect of a dual combination of noninsulin anti-hyperglycemic agents on lipids is moderate to small, with metformin + DPP-4 inhibitor and metformin + GLP-1 agonist showing consistent beneficial effects on LDL cholesterol, HDL cholesterol, triglycerides and total cholesterol. Future trials are needed to confirm these findings.

Diabetes and Mental Health

Diabetes and Mental Health