Use Of Antihyperglycemic Agents Research Articles

Laparoscopic Roux-en-Y gastric bypass for excess weight and diabetes: a multicenter retrospective cohort study in China

Aim: The aims of this study were to better understand the outcomes of Roux-en-Y gastric bypass (RYGB) surgery in patients across multiple hospitals in China along with patients with type 2 diabetes mellitus (T2DM) and to explore the potential preoperative predictors of diabetes outcomes after RYGB. Methods: This was a retrospective cohort study in Chinese patients who underwent laparoscopic RYGB at five Chinese hospitals from April 2009 to December 2014 and returned for follow-up approximately one-year post-surgery. The STROCSS guideline checklist was applied. Results: In total, 130 patients underwent RYGB: 85 males and 45 females; age, 43.4 ± 11.3 years; and preoperative body mass index (BMI), 33.1 ± 9.0 kg/m2. Of those, 103 (79.2%) had T2DM duration of 6.6 ± 4.7 years and pre-RYGB HbA1c of 8.1 ± 1.9%. Among the patients with T2DM, glycemic control (HbA1c < 7.0%) increased from 28.7% before surgery to 79.3% at 12 months post-procedure, with a concurrent reduction in the use of anti-hyperglycemic agents, including a reduction in insulin requirement from 55.4% to 27.0%. The percentage of excess weight loss was -42.8 ± 44.2%. Among 71 patients with T2DM and data about remission status, 14 (19.7%) achieved T2DM remission at 12 months post-surgery. Age and duration of T2DM were lower in the remission group, while baseline BMI and weight were higher compared with the non-remission group. Conclusion: RYGB may be effective for weight loss and T2DM control in Chinese patients, and outcomes are consistent with the literature in Western populations. Younger patients with T2DM and with a higher BMI pre-surgery and shorter duration of T2DM were more likely to achieve T2DM remission.

PSUN195 Use of Anti-Hyperglycemic Agents Before and After Roux-en-y Gastric Bypass (RYGB) and Laparoscopic Sleeve Gastrectomy (LSG)

Abstract Introduction Currently there is no standardized approach or guideline regarding use of anti-hyperglycemic agents in the pre and postoperative diabetes management of patients undergoing bariatric surgery. There is a need to investigate the efficacy of current anti-hyperglycemic medications in the context of bariatric surgery. Methods The primary aim was to describe the patterns of use of anti-hyperglycemic agents in the pre-operative and post-operative period in patients undergoing bariatric surgery. A secondary aim was to evaluate the association between various anti-hyperglycemic agents on diabetes control. This study was a single-center retrospective chart review that identified patients with type 2 diabetes and obesity who underwent bariatric surgery between the years 2013 to 2020. Patients were identified using ICD-10 codes and surgical CPT codes. Demographic data, anthropometric data, and markers of diabetes were collected immediately preoperatively, day of surgery, 6 months postoperatively and 1-year postoperatively. Results 132 patients with obesity and T2DM underwent RYGB (n=61) and LSG (n=71). The RYGB group had significantly higher pre-surgery weight (132+30 kg vs 125+27kg, P=0.066), BMI (45.0+6 kg/m2 vs 42.7+5.7 kg/m2, P=0.013), and HbA1c (7.44+0.9% vs 7.2+0.7%, P=0.062) compared to the LSG group. Post-surgical weight loss was greater in the RYGB group 38+14 kg (29% TBWL) compared to the LSG group 30+14 kg (25% TBWL) (p=0.004) at 1-year. HbA1c reduction was significantly better in RYGB group 1.52% (n=42) compared with the LSG group 1.05% (n=47) (P=0.034) at 1-year. Medication analysis prior to surgery showed that 88% (n=113) were taking at least 1 anti-hyperglycemic agent, with a mean of 1.6 medications per patient. The last dose of all anti-hyperglycemic agents was the day prior to surgery. In the immediate postoperative course, no agents were initiated in both groups. Post-surgical medication analysis at 1-year showed complete elimination of anti-hyperglycemic agent use in 42% (n=26) of RYGB group and 59% (n=42) in LSG group. Patients on metformin prior to bariatric surgery had a greater delta 1-year post-operative HbA1c (mean -0.558+0.2786) (p=0.05) compared to patients not on metformin in LSG group. This trend was not seen in patients on metformin therapy in the RYGB group. Patients on insulin prior to bariatric surgery had a positive delta 1-year post-operative HbA1c (mean 0.781+0.2761) (p=-.007) compared to patients not on insulin in LSG group. These trends were not seen in patients using either metformin or insulin therapy in the RYGB group. Conclusion In patients with T2DM undergoing bariatric surgery, metformin monotherapy was associated with greater post-operative 1-year HgA1c reduction in LSG group. This suggests possible benefit from treatment with metformin in patients undergoing LSG bariatric surgery. Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

Are we there yet? Increasing use of cardioprotective antihyperglycemic agents in patients with T2D and CVD or CV risk in the United States

Objective To report on the use of antihyperglycemic agents (AHAs) by age (i.e. <65, ≥65 years) in patients with type 2 diabetes (T2D) and cardiovascular disease (CVD) or cardiovascular risk (CV risk) factors in the United States. Methods Patients with T2D and CVD (CVD cohort) or T2D and an additional CV risk factor without pre-existing CVD (CV risk cohort) were identified from 2015 to 2019 in a claims database. Patients were followed from their first observed CVD diagnosis or CV risk factor for each year they were continuously enrolled or until occurrence of a CVD diagnosis (CV risk cohort only). Classes of AHAs received were reported by year, cohort, and age group. Results From 2015 to 2019, the percentage of patients <65 years on glucagon-like peptide-1 receptor agonists (GLP-1 RAs) increased (CVD: 9–17%, CV risk: 9–17%) and was approximately twice that of those ≥65 years (CVD: 4–8%, CV risk: 4–8%); the percentage of patients <65 years on sodium-glucose cotransporter-2 (SGLT2) inhibitors increased (CVD: 11–16%, CV risk: 11–17%) and was approximately triple that of those ≥65 years (CVD: 3–6%, CV risk: 4–7%). Conclusions The use of GLP-1 RAs and SGLT2 inhibitors increased during the study period; however, most patients did not receive these medications. Patients aged ≥65 years were particularly disadvantaged.

Characterization of alpelisib-associated hyperglycemia in metastatic breast cancer.

1016 Background: For women with metastatic hormone receptor (HR)-positive, human epidermal growth factor 2 (HER2)-negative breast cancer, the combination of alpelisib and fulvestrant improves progression-free survival in those with PIK3CA mutations. Hyperglycemia is a major toxicity of PI3K inhibitors including alpelisib, which limits the clinical efficacy of these drugs due to interrupted/reduced dosing and discontinuation. In the SOLAR-1 trial that led to the Food and Drug Administration (FDA) approval of alpelisib, over 60% of patients developed hyperglycemia of any grade, and over 36% developed grade 3-4 hyperglycemia. Here we describe the incidence and treatment of alpelisib-associated hyperglycemia in a single center cohort. Methods: Patients with metastatic breast cancer who received alpelisib on a clinical trial or as part of standard care from 2013-2021 at Memorial Sloan Kettering Cancer Center were included in this retrospective study. Patient and tumor characteristics and pre-treatment body mass index (BMI), hemoglobin A1c, and serum glucose levels were abstracted from medical records. Alpelisib dose interruptions, reductions, or discontinuation was recorded as well as endocrinology consultation and use of anti-hyperglycemic agents. Date of progression and/or death were recorded where applicable. Results: 247 patients were included in this study, among whom 245 (99.1%) were female and 198 (80.1%) were white. 100 (40.5%) were treated on a clinical trial. Median baseline BMI was 25.4 kg/m2. Among 164 patients with baseline hemoglobin A1c levels available, 93 (56.7%) patients had normal hemoglobin A1c, 54 (32.9%) had prediabetes, and 17 (10.4%) had diabetes. 152 patients (61.5%) developed hyperglycemia of any grade; 56 (22.7%) developed grade 3 and 16 (6.5%) developed grade 4 hyperglycemia. The median time to onset of hyperglycemia was 16 days. BMI ≥25 kg/m2 or hemoglobin A1c ≥5.7% were strongly predictive of development of any-grade hyperglycemia ( p= 0.036 and p&lt; 0.001, respectively) and grade 3-4 hyperglycemia ( p&lt; 0.001 for both). Among those who developed hyperglycemia, 101 (40.9%) received treatment; 69 patients (27.9%) required only 1 anti-hyperglycemic agent whereas 9 (3.6%) required ≥3 anti-hyperglycemic agents. 49 (19.8%) were referred for endocrinology consult. In 66 patients (26.7%), alpelisib was held until resolution of hyperglycemia; 42 patients (17%) required dose reductions, and 11 (4.5%) discontinued alpelisib due to hyperglycemia. There was no significant difference in progression-free survival by hyperglycemia status or severity of hyperglycemia. Conclusions: Overweight BMI and hemoglobin A1c in the prediabetes or diabetes range were strongly predictive of developing alpelisib-associated hyperglycemia. Management of these co-morbidities prior to alpelisib treatment should be strongly considered.

Covid 19 May Limit the Use of Anti-hyperglycemic Agents. Does it Call for the Development of New Anti-hyperglycemic Agents?

Diabetes mellitus has been identified as a major risk factor for developing severe COVID 19 complications. In this review article, the efforts were directed to provide insights and the possible extent to which some diabetic pharmacological interventions may exacerbate COVID 19 or may not be idyllic options for COVID 19 patients. Articles reviewed were identified using the Google scholar database, and search was done using the English language. Anti-hyperglycemic is associated with undesirable effects including episodes of hypoglycemia, diarrhea, lactic acidosis, and increased risks of cardiovascular and hepatic hazards. These undesirable effects associated with the anti-hyperglycemic agents possess a threat of developing severe COVID19 complications Therefore, this calls for more studies to understand the extent of the risks these agents possess in diabetic COVID 19 patients. Almost all the anti-hyperglycemic agents have the potential to worsen COVID 19, despite their class. COVID 19 may limit the options in terms of available anti-hyperglycemic agents which may not heighten the risk of developing severe COVID 19 complications. The research towards the discovery and development of new compounds and also new therapeutic targets for hyperglycemia should be encouraged and welcome.

851-P: Are We There Yet? Increasing Use of Cardioprotective Antihyperglycemic Agents in Patients with T2D and CVD or CV Risk in the U.S.

There is limited US real-world evidence on changes in use of antihyperglycemic agents (AHA) by age in patients with T2D and CVD or CV risk. Patients with T2D and CVD or T2D and an additional CV risk factor were identified from 2015-2019 in the MarketScan data. Patients with continuous enrollment for the calendar year of the index date (first observed CVD diagnosis [Dx]/CV risk factor) and no CVD Dx before or in the same year as the index date (CV risk cohort only) were included. Patients were followed for each year they were continuously enrolled or until a CVD Dx (CV risk cohort). AHA classes received in each year were reported by cohort and age group ( Disclosure R. Mody: Employee; Self; Eli Lilly and Company. J. Meyers: None. M. Yu: Employee; Self; Lilly Diabetes, Employee; Spouse/Partner; LifeLabs, Stock/Shareholder; Self; Lilly Diabetes, Stock/Shareholder; Spouse/Partner; Lilly Diabetes. J. A. Levine: Employee; Self; Eli Lilly and Company, Stock/Shareholder; Self; Eli Lilly and Company. K. Davis: Research Support; Self; AstraZeneca, Eisai Inc., Eli Lilly and Company, Novartis Pharmaceuticals Corporation, Pfizer Inc., Sanofi, Vertex Pharmaceuticals Incorporated.

982-P: Use of Antihyperglycemic Agents (AHA) with Cardioprotective Benefit in Older Patients with T2D and CVD or CV Risk Factors

There is limited published evidence on population-level use of AHA among patients (pts) ≥65 years with T2D and CVD or CV risk factors in the US. Pts ≥65 years with T2D and CVD/CV risk factors and continuous enrollment in a Medicare Advantage and Prescription plan were identified from claims (Humana Research Database) between 2015 and 2019. The CVD/CV risk cohorts included pts with ≥1 claim with CVD/CV risk factors after T2D diagnosis date (same or subsequent years) between 2015 and 2019. The CV risk cohort did not have any CVD diagnosis prior to inclusion and were included until diagnosed with CVD. For both cohorts, pts were continuously enrolled during the calendar year being evaluated. CVD and CV risk cohorts included 477,801 and 661,550 pts respectively. During the study period, in both cohorts, the use of cardioprotective AHA classes (GLP-1 RAs and SGLT-2is) was Disclosure R. Mody: Employee; Self; Eli Lilly and Company. S. Cowburn: None. M. Yu: Employee; Self; Lilly Diabetes, Employee; Spouse/Partner; LifeLabs, Stock/Shareholder; Self; Lilly Diabetes, Stock/Shareholder; Spouse/Partner; Lilly Diabetes. R. Nair: Employee; Self; Humana. M. Konig: Employee; Self; Eli Lilly and Company. T. G. Prewitt: None.

The triterpene, methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), attenuates high glucose-induced oxidative damage and apoptosis by improving energy metabolism

BackgroundHyperglycemia-induced cardiovascular dysfunction has been linked to oxidative stress and accelerated apoptosis in the diabetic myocardium. While there is currently no treatment for diabetic cardiomyopathy (DCM), studies suggest that the combinational use of anti-hyperglycemic agents and triterpenes could be effective in alleviating DCM. HypothesisTo investigate the therapeutic effect of methyl-3β-hydroxylanosta-9,24-dien-21-oate (RA3), in the absence or presence of the anti-diabetic drug, metformin (MET), against hyperglycemia-induced cardiac injury using an in vitro H9c2 cell model. MethodsTo mimic a hyperglycemic state, H9c2 cells were exposed to high glucose (HG, 33 mM) for 24 h. Thereafter, the cells were treated with RA3 (1 μM), MET (1 μM) and the combination of MET (1 μM) plus RA3 (1 μM) for 24 h, to assess the treatments therapeutic effect. ResultsBiochemical analysis revealed that RA3, with or without MET, improves glucose uptake via insulin-dependent (IRS-1/PI3K/Akt signaling) and independent (AMPK) pathways whilst ameliorating the activity of antioxidant enzymes in the H9c2 cells. Mechanistically, RA3 was able to alleviate HG-stimulated oxidative stress through the inhibition of reactive oxygen species (ROS) and lipid peroxidation as well as the reduced expression of the PKC/NF-кB cascade through decreased intracellular lipid content. Subsequently, RA3 was able to mitigate HG-induced apoptosis by decreasing the activity of caspase 3/7 and DNA fragmentation in the cardiomyoblasts. ConclusionRA3, in the absence or presence of MET, demonstrated potent therapeutic properties against hyperglycemia-mediated cardiac damage and could be a suitable candidate in the prevention of DCM.

Abstract 16177: Race and Sex-specific Long-term Risk of Incident Heart Failure in Adults Stratified by Fasting Glucose Level: Lifetime Risk Pooling Project

Introduction: While the association of diabetes with heart failure (HF) is well-established, the long-term risk (LR) of incident HF with prediabetes across the life course is not known. Furthermore, race-sex disparities in LR of HF across categories of fasting plasma glucose (FPG) has not been described. To inform HF preventive strategies, we compared the race- and sex-specific LR of HF across categories of FPG in adults. Methods: Individual-level data from adults free of baseline HF was pooled from 6 population-based cohorts stratified by baseline age (40-59, 60-79 years) and race-sex groups. We defined FPG status as normal (&lt;100 mg/dL), prediabetes (FPG 100-125 mg/dL) and diabetes (FPG ≥126 mg/dL or use of antihyperglycemic agents). Modified Kaplan-Meier analysis was performed by FPG strata to estimate the LR of HF (30-year in middle-aged and 20-year in older adults) adjusted for the competing risk of non-HF death. We estimated adjusted hazard ratios (aHR) for HF in each FPG strata using Cox proportional regression models. Results: Of the 40,117 participants, 24% were black and 56% were women. During 638,910 person-years of follow-up, there were 4,846 cases of incident HF. In middle-aged adults, the LR of HF was significantly higher among individuals with prediabetes (6.1 [4.8, 7.4] to 14.4 [9.6, 19.2]%) compared with normal FPG (3.5 [3.0, 4.1] to 11.7 [9.1, 14.3]%). In older adults with prediabetes compared with normal FPG, LR of HF was significantly higher in white men (13.5 [12.0, 14.9]% vs 10.4 [9.2, 11.6]%) and women (12.2 [10.8, 13.6]% vs 7.8 [6.9, 8.7]%) but not in black men (12.2 [9.0, 15.3]% vs 14.6 [11.6, 17.6]%) or women (13.5 [10.1, 16.8]% vs 11.7 [9.4, 14.0]%). Race-sex specific aHR for HF across FPG strata are shown in the table. Conclusions: Compared with normal FPG, prediabetes was associated with significantly greater LR of HF in middle-aged but not in older adults. Of all groups, black women with diabetes qualitatively had a disproportionately higher LR of HF.

ASIAN PACIFIC SOCIETY OF NEPHROLOGY CLINICAL PRACTICE GUIDELINE ON DIABETIC KIDNEY DISEASE - EXECUTIVE SUMMARY.

Introduction: COVID-19 is now a global pandemic affecting millions of people Patients on dialysis are at an increased risk to COVID-19 infection due to their exposure in the health care setting Strategies for infection control and prevention are also being implemented in the dialysis units because of the increased risk of virus transmission within the unit Objective: Describe the different measures and strategies done to mitigate the spread of COVID-19 outbreak in a hospital based dialysis centre Methods: Review of the epidemic course with contact tracing was done from March 14 to May 14, 2020 in the dialysis unit of a tertiary hospital Results: Of 167 haemodialysis patients, 20 were considered COVID-19 suspects Eight tested positive-2 were traced to be exposed with the first confirmed case, 2 were handled by a COVID-19 infected healthcare worker (HCW) who was asymptomatic at time of contact while 2 asymptomatic patients tested positive during mass screening Two of 67 HCWs tested positive were exposed to patients Key interventions during the course of the outbreak included: mass testing of patients and HCWs after identifying 6 patients and 2 HCWs infected with COVID-19 using nasopharyngeal/oropharyngeal swabs by RT-PCR;dialysis of COVID-19 confirmed and suspected cases in isolation rooms separate from the dialysis unit (instead of cohorting);provision of adequate protective personal equipment for HCWs and surgical masks for all patients, environmental disinfection especially in the waiting area with strict social distancing and screening for signs and symptoms at the entrance of the unit Conclusion: Infection control strategies are needed to manage the spread of COVID-19 in dialysis centres These infection prevention measures should be implemented at the first indication of transmission in the area and should be maintained for the duration of the pandemic and until the area show no more reports of transmission

Selecting antihyperglycemic agents with proven safety: A must in COVID-19 era

The use of antihyperglycemic agents with proven cardiorenal benefits from cardiovascular outcome trials (CVOTs) and proven safety derived from thorough QTc trials be considered preferentially in the management of type 2 diabetes.

Can Long-term Treatment of Obstructive Sleep Apnea With CPAP Improve Glycemia and Prevent Type 2 Diabetes?

Obstructive sleep apnea (OSA) is a prevalent sleep disorder caused by intermittent partial or complete collapse of the upper airway during sleep resulting in intermittent hypoxemia and hypercapnia, sleep fragmentation, increased oxidative stress, and systemic inflammation. The prevalence of moderate-to-severe OSA in the general population, estimated at 23.4% in women and 49.7% in men, has increased over the past few decades (1,2), due in part to the obesity epidemic (3). Multiple observational studies have reported an association between OSA, insulin resistance, and increased risk of incident type 2 diabetes (4,5). In a meta-analysis, the presence of OSA was independently associated with a 1.35-fold increase in the risk of developing type 2 diabetes (4). In addition to being a risk factor for developing type 2 diabetes, OSA is highly prevalent in adults with type 2 diabetes, with prevalence estimates between 58% and 86%, with moderate-to-severe OSA being present in 25–59% of individuals (4). Although increasing severity of OSA has been associated with worsened glycemic control (6), continuous positive airway pressure (CPAP), the gold standard treatment of OSA, has not been consistently shown to improve glycemic control or reduce insulin resistance in clinical trials in which CPAP was used for 1–6 months (4,7–10). Multiple factors may contribute to the heterogeneity of the results, including different levels of CPAP adherence, various durations of CPAP therapy, background glycemic control, and the use of antihyperglycemic agents, the number of which has been ever increasing. In well-controlled laboratory experiments, however, there is evidence that short-term CPAP use with ensured compliance of 8 h nightly for 1–2 weeks results in improved …

SUN-LB115 Is the Stepping-Down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-Controlled Diabetes on Advanced Insulin Therapy?

In the traditional step-up approach, patients with poorly-controlled T2DM are eventually advanced to multiple daily insulin injections (MDI). However, some on advanced insulin therapy (AIT) continue to have poor control due to poor compliance with MDI and fear of insulin-induced weight gain. The recent guidelines recommend the use of anti-hyperglycemic agents with weight loss benefits, such as SGLT2i or GLP1 RA, with basal insulin before the patients are advanced to MDI. Objective: To determine if de-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin by using the stepping-down approach is a better option than MDI in obese patients with poorly- controlled T2DM on AIT. Research Design: This pilot, prospective, randomized, open-label, controlled, parallel-group trial enrolled 22 obese patients with T2DM on AIT, who had BMI ≥30 kg/m2, A1c >8% and eGFR >45. Patients were randomized to either intervention (Step-Down) or control (MDI) group. In the control group, the patient was advised to remain on MDI. In the intervention group, all prandial insulin injections were discontinued; but the patient remained on the basal insulin and metformin to which SGLT2i, Empagliflozin, and GLP1 RA, Dulaglutide, were added. They were followed up for 16 weeks. The primary outcome was A1c change and secondary outcomes were the change in fasting BG, weight, BP, HR, fasting lipids, serum Na and K, serum Cr, liver enzymes, CBC and Diabetes Medications Satisfaction (DM-SAT) scores at 16 weeks. Results: There was no difference in A1c between 2 groups (10.36% vs 9.69%;p=0.171) at baseline. However, A1c was significantly lower at 4 weeks (9.54% vs 7.31%; p=0.0088) and 16 weeks (9.7% vs 8.25%; p<0.001) in intervention group (n=10). Compared to baseline, in the control group (n=8), there was no significant change at secondary outcome variables except slightly higher SBP at 16 weeks. In intervention group, compared to baseline, there was a significant decrease in weight (-16.38 Lbs; p=0.003), BMI (-3.06; p<0.001), LDL cholesterol (-15.7 mg/d; p=0.0378), total cholesterol (-18.5 mg/dL; p=0.0386), total daily insulin dose (-57.3 units; p<0.001) and a significant improvement in DM-SAT patient satisfaction 0-100 scores - total score (+45.3; p <0.001) and subscale scores (Convenience +35.28, p =0.019; Lifestyle +35.8, p=0.0052; Medical control +51.3, p<0.001; Wellbeing +47.2,p=0.0091) at 16 weeks. Conclusions: De-escalating from AIT to the combined use of metformin, SGLT2i, GLP1 RA and basal insulin in obese patients with poorly-controlled T2DM by using the stepping-down approach results in the significant improvement in glycemic control, weight loss, and significantly higher patient satisfaction. This noble stepping-down approach may be a better option than continuing MDI in such patients. This pilot study result needs to be confirmed with a larger trial. ClinicalTrials ID: NCT02846233

Effect of alirocumab on individuals with type 2 diabetes, high triglycerides, and low high-density lipoprotein cholesterol

BackgroundMixed dyslipidemia [elevated non-high-density lipoprotein cholesterol (non-HDL-C) and triglycerides (TGs), and decreased HDL-C] is common in type 2 diabetes mellitus (T2DM) and is associated with increased cardiovascular risk. Non-HDL-C and apolipoprotein B (ApoB) are the preferred therapeutic targets for mixed dyslipidemia. Alirocumab is a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 (PCSK9) that effectively reduces low-density lipoprotein cholesterol (LDL-C), non-HDL-C, ApoB, and lipoprotein(a) (Lp[a]), and is well-tolerated in individuals with T2DM.MethodsThe previously reported open-label ODYSSEY DM-DYSLIPIDEMIA trial data demonstrated the effects of alirocumab on individuals with non‐HDL-C ≥ 100 mg/dL and TGs ≥ 150 and < 500 mg/dL receiving stable maximally tolerated statin (n = 413). This post hoc subgroup analysis of the primary trial investigated the effects of alirocumab [75 mg every 2 weeks (Q2W) with possible increase to 150 mg Q2W at Week 12] versus usual care [ezetimibe, fenofibrate, or no additional lipid-lowering therapy (LLT)] on non-HDL-C and other lipids in individuals with T2DM and baseline TGs ≥ 200 mg/dL and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women).ResultsAlirocumab significantly reduced non-HDL-C [LS mean difference (standard error (SE)), − 35.0% (3.9)], ApoB [LS mean difference (SE), − 34.7% (3.6)], LDL-C [LS mean difference (SE), − 47.3% (5.2)], LDL particle number [LS mean difference (SE), − 40.8% (4.1)], and Lp(a) [LS mean difference (SE), − 29.9% (5.4)] versus usual care from baseline to Week 24 (all P < 0.0001). Results were similar for alirocumab versus usual care. TG reductions were similar between alirocumab and usual care (no significant difference), but greater with fenofibrate versus alirocumab (P = 0.3371). Overall, alirocumab significantly increased HDL-C versus usual care [LS mean difference (SE), 7.9% (3.6); P < 0.05], although differences with alirocumab versus ezetimibe or fenofibrate were non-significant. Most individuals receiving alirocumab achieved ApoB < 80 mg/dL (67.9%) and non-HDL-C < 100 mg/dL (60.9%). Adverse event frequency was similar between alirocumab (67.2%) and usual care (70.7%). Additionally, no clinically relevant effect of alirocumab on change in glycemic parameters or use of antihyperglycemic agents was observed.ConclusionsAlirocumab is an effective therapeutic option for individuals with T2DM, TGs ≥ 200 mg/dL, and HDL-C < 40 mg/dL (men) or < 50 mg/dL (women). Atherogenic lipid (ApoB and non-HDL) reductions were greater with alirocumab than ezetimibe, fenofibrate, or no LLT. Consistent with previous studies, alirocumab was generally well tolerated.Trial registration Clinicaltrials.gov, NCT02642159. Registered December 24, 2015, https://clinicaltrials.gov/ct2/show/NCT02642159

Retrospective Cohort Analysis of the Reduced Burden of Hypoglycemia Associated with Dipeptidyl Peptidase-4 Inhibitor Use in Patients with Type 2 Diabetes Mellitus.

IntroductionThe use of antihyperglycemic agents (AHA), especially insulin and sulfonylureas (SU), is a risk factor for hypoglycemia. Despite the significant clinical and economic burdens associated with hypoglycemia and the decreasing use of SU in favor of other oral AHA, relatively little is known about hypoglycemia trends specific to the use of non-insulin AHA. We sought to estimate annual hypoglycemia event rates and costs among patients with type 2 diabetes mellitus (T2DM) who started either SU or dipeptidyl peptidase-4 inhibitors (DPP-4i) and to predict rates and costs in the absence of DPP-4i.MethodsTruven’s MarketScan Commercial Claims database was used to estimate hypoglycemia event rates and costs from 2007 to 2013. Hypoglycemia, defined using diagnosis codes, was assessed during the 12 months following SU (n = 245,201) or DPP-4i (n = 176,786) initiation by adults with T2DM. Coefficients from a Poisson regression model used to estimate the impact of patient characteristics on hypoglycemia rates for patients who started SU were used to predict rates for patients who started DPP-4i had they started SU instead.ResultsHypoglycemia events per 100 patient-years (costs per event) ranged from 5.4 ($565) in 2007 to 10.4 ($1154) in 2013 for patients starting SU; rates (costs) for patients starting DPP-4i ranged from 3.2 ($308) in 2007 to 6.4 ($482) in 2013. Predicted hypoglycemia rates would have been 5.3–9.9 per 100 person-years for patients who started DPP-4i had they started SU instead. Starting DPP-4i, rather than SU, would have resulted in national savings of $750.3 million in healthcare costs due to avoided hypoglycemia events during this period.ConclusionsHypoglycemia rates and costs were consistently higher for patients who started SU rather than DPP-4i. The overall burden of hypoglycemia could be lowered substantially in the USA if, when feasible, patients with T2DM initiate DPP-4i instead of SU.FundingMerck & Co., Inc., Kenilworth, NJ USA.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0512-3) contains supplementary material, which is available to authorized users.

Predictive Value of Acute Pancreatitis Diagnosis Code in Diabetic Patients Is Similar to Non-Diabetic Patients

Introduction: Diabetes Mellitus (DM) has a bidirectional relationship with acute pancreatitis (AP). However, the role of prevalent DM on the course and severity of AP is less clear. Administrative datasets are useful in large cohorts to study outcomes and predictors of severity in AP. Since patients with DM have frequent elevations in serum pancreatic enzymes, the utility of administrative data in diabetic patients to study AP related outcomes in diabetic patients is unclear. We hypothesized that the positive predictive value (PPV) of diagnosis code for AP will be suboptimal in AP patients with prevalent DM when compared with non-diabetic patients. Methods: We retrospectively reviewed data from all unique patients who received a primary inpatient discharge code of AP (ICD-9 577.0) at the University of Pittsburgh Medical Center Presbyterian Hospital between June 2009 and August 2014. Demographics, etiology and clinical variables were obtained by chart review. Patients were stratified into diabetic and non-diabetic groups based on the presence of DM diagnosis in the electronic record, use of antihyperglycemic agents, or Hemoglobin A1c ≥6.5% at or before hospitalization for AP. A diagnosis of AP was established by the presence of at least 2 of 3 features (upper abdominal pain, serum pancreatic enzymes to ≥3-fold the reference limit of normal, and imaging findings consistent with AP). Results: 579 patients received a primary inpatient discharge diagnosis of AP during the study period. 161 (27.8%) had prevalent DM. Of these 161 patients, 124 met the diagnostic criteria for AP (PPV=0.77), which was similar to the PPV for AP diagnosis in patients without DM (336/418, PPV=0.80; p = 0.47). AP patients with prevalent diabetes were similar to those without diabetes in age, sex, ethnicity, tobacco use, and presentation with a sentinel episode of AP. Gallstones were the most common cause of AP in both groups. Diabetic patients were significantly more likely to have hypertriglyceridemia as the etiology, while alcoholic pancreatitis was more common in non-diabetic patients. These findings were similar in a subset analysis for patients who presented with a sentinel episode of AP. Conclusion: About 1 in 5 patients who receive a primary inpatient diagnosis of AP do not meet the recommended definition for diagnosis. The etiologic spectrum of AP in diabetic patients differs from nondiabetic patients. The PPV for diagnosis code for AP does not differ based on prevalent diabetic status.63_A Figure 1. No Caption available.63_B Figure 2. No Caption available.

Effect of Antihyperglycemic Agents on Hemoglobin A1c Level in Type 2 Diabetes Mellitus Patients

Background : Type 2 diabetes mellitus (T2DM) patients require continuous lifelong attention to pharmacotherapy to achieve and maintain optimal glucose control, which can be monitored through measuring HbA1c. This study aimed to see the comparrison of HbA1c levels before and after a minimum of two months use of antihyperglycemic agents in patients with T2DM. Methods : This analytical cross-sectional study used medical records of patients with T2DM in the center of outpatient medical records at the Department of Clinical Pathology, Dr. Hasan Sadikin General Hospital, in 2013. Sampling was conducted using consecutive sampling technique. The data analysis used the paired t-test and Wilcoxon test for not normal data distribution. Results : Before and after a minimum of two months use of antihyperglycemic agents, HbA1c concentration was 7.15% (6.1–12.2) and 7.3% (5.9–11.9) respectively. Statistically, the difference of HbA1c concentration of T2DM patients between those period was not significant (0.15%; p=0,812). Mean HbA1c concentration was found with greatest decrease in patients treated with sulfonylurea (2.25%), followed by insulin (0.1%). There were increases in mean HbA1c concentration in patients treated with metformin (0.05%), metformin+insulin (1.1%), sulfonylurea +metformin (0.6%), sulfonylurea+alpha-glucosidase inhibitor (1.1%), and sulfonylurea + metformin + alpha-glucosidase inhibitor (0.05%). Conclusions : There is no significant difference of HbA1c levels before and after two months to two years use of antihyperglycemic agents in T2DM patients. This result showed the importance of comprehensiveness in T2DM therapy. The therapy should not merely consist of antihyperglycemic medication alone, but also physical exercise, lifestyle modification, and diet control.

Antihyperglycemic agent therapy for adult patients with type 2 diabetes mellitus 2017: a position statement of the Korean Diabetes Association.

In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.

Insulin therapy for adult patients with type 2 diabetes mellitus: a position statement of the Korean Diabetes Association, 2017.

The Korean Diabetes Association (KDA) has regularly updated its Clinical Practice Guidelines. In 2017, the KDA published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). Growing evidence from new multinational clinical trials using novel and traditional insulin analogues has also been accumulated. Following global trends, many results of clinical trials, especially concerning the clinical efficacy and safety of insulin therapy, have been published about Korean patients with T2DM. After a systematic search of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the initiation, choice, and intensification of insulin and created an insulin treatment algorithm for the first time to guide physicians caring for adult Korean patients with T2DM.

Antihyperglycemic Agent Therapy for Adult Patients with Type 2 Diabetes Mellitus 2017: A Position Statement of the Korean Diabetes Association.

In 2017, the Korean Diabetes Association (KDA) published a position statement on the use of antihyperglycemic agents for patients with type 2 diabetes mellitus (T2DM). The KDA regularly updates its Clinical Practice Guidelines, but since the last update in 2015, many results from clinical trials have been introduced, and domestic data from studies performed in Korean patients with T2DM have been published. Recently, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations. Additionally, new data from clinical trials using dipeptidyl peptidase 4 inhibitors and thiazolidinediones in Korean patients with T2DM were added. Following a systematic review and assessment of recent evidence, the KDA updated and modified its clinical practice recommendations regarding the use of antihyperglycemic agents and revised the treatment algorithm for Korean adult patients with T2DM.