Greater Glycemic Burden Is Associated with Further Poorer Glycemic Control in Newly-Diagnosed Type 2 Diabetes Mellitus Patients

Aims: hyperglycemia impairs pancreatic β-cell function instantly, also known as glucotoxicity. It is unknown whether this insult is temporary or sustained, and little real-world evidence needs to reflect the relationship between hyperglycemic burden, per se, and glycemic durability. Materials and Methods: a retrospective observational cohort study was conducted to recruit newly-diagnosed type 2 diabetes mellitus (T2DM) patients. Durability was defined as the episode from first glycated hemoglobin A1c (HbA1c) below 7.0% to where it exceed 8.0% (with treatment failure) or where study ended (without treatment failure). Glycemic burden was defined with the area above a burden value line (HbA1c = 6.5%) but under the HbA1c curve (AUC), and it was then divided into two compartments with the demarcation timepoint once HbA1c was treated below or equal to 7.0%; the former AUC’ represented the initial insult; the latter AUC” represented the residual part. Multivariable regression models assessed factors associated with durability in whole participants and two distinct subgroups: patients with baseline HbA1c > 7.0% or ≤7.0%. Results: 1048 eligible participants were recruited and analyzed: 291 patients with treatment failure (durability 26.8 ± 21.1 months); 757 patients without treatment failure (durability 45.1 ± 31.8 months). Besides age, glycemic burden was the only constant determinant in the two subgroups. AUC’ or AUC” increased treatment failure, respectively, in baseline HbA1c > 7.0% or ≤7.0% subgroup [per 1%/90 days hazard ratio (95% confidence interval): 1.026 (1.018–1.034) and 1.128 (1.016–1.253)]. Other determinants include baseline HbA1c, initial OAD, and education level. Conclusions: in patients with newly-diagnosed T2DM, glycemic durability was negatively associated with greater glycemic burden.

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

<b>Objective:</b> Current guidelines recommend prescribing SGLT-2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. <p><b>Methods:</b> In the Dapagliflozin Effect on Cardiovascular Events (DECLARE)-TIMI 58 trial 17,160 patients with type 2 diabetes were randomized to dapagliflozin or placebo for a median follow up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population, and with dapagliflozin vs. placebo in HbA1c subgroups were studied by Cox regression models.</p> <p><b>Results:</b> In the overall population, increasing HbA1c was associated with higher risk of cardiovascular death or hospitalization for heart failure (CVD/HHF), major adverse cardiovascular events (MACE; CVD, myocardial infarction, ischemic stroke) and of the cardiorenal outcome (adjusted HR [95% CI] 1.12 [1.06-1.19], 1.08 [1.04-1.13] and 1.17 [1.11-1.24] per 1% increase respectively). Elevated HbA1c was associated with an increased risk for MACE and for the cardiorenal outcome significantly more in patients with multiple risk factors (MRF), vs. patients with established ASCVD (P-interaction 0.0064 and 0.0093 respectively). Dapagliflozin led to a decrease in the risk of CVD/HHF, HHF and the cardiorenal outcome vs. placebo with no heterogeneity by baseline HbA1c (P-interaction >0.05).</p> <p><b>Conclusions</b>: High HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c<7%.</p>

Association of Baseline HbA1c With Cardiovascular and Renal Outcomes: Analyses From DECLARE-TIMI 58

OBJECTIVE Current guidelines recommend prescribing SGLT2 inhibitors to patients with type 2 diabetes and established or at high risk for atherosclerotic cardiovascular disease (ASCVD), irrespective of HbA1c levels. We studied the association of HbA1c with cardiovascular and renal outcomes and whether the benefit of dapagliflozin varies by baseline HbA1c. RESEARCH DESIGN AND METHODS In the Dapagliflozin Effect on Cardiovascular Events trial (DECLARE-TIMI 58), 17,160 patients with type 2 diabetes were randomly assigned to dapagliflozin or placebo for a median follow-up of 4.2 years. Cardiovascular and renal outcomes by baseline HbA1c in the overall population and with dapagliflozin versus placebo in HbA1c subgroups were studied by Cox regression models. RESULTS In the overall population, higher baseline HbA1c was associated with a higher risk of cardiovascular death or hospitalization for heart failure (HHF); major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and ischemic stroke; and cardiorenal outcomes (adjusted hazard ratios 1.12 [95% CI 1.06–1.19], 1.08 [1.04–1.13], and 1.17 [1.11–1.24] per 1% higher level, respectively). Elevated HbA1c was associated with a greater increased risk for MACE and cardiorenal outcomes in patients with multiple risk factors (MRF) than in established ASCVD (P-interaction = 0.0064 and 0.0093, respectively). Compared with placebo, dapagliflozin decreased the risk of cardiovascular death/HHF, HHF, and cardiorenal outcomes, with no heterogeneity by baseline HbA1c (P-interaction &gt; 0.05). CONCLUSIONS Higher HbA1c levels were associated with greater cardiovascular and renal risk, particularly in the MRF population, yet the benefits of dapagliflozin were observed in all subgroups irrespective of baseline HbA1c, including patients with HbA1c &lt;7%.

Potential bias of preoperative intravitreal anti-VEGF injection for complications of proliferative diabetic retinopathy

Purpose Intravitreal anti-VEGF injection (IVI) is administered before vitrectomy to assist management of proliferative diabetic retinopathy (PDR)-related complications. In the clinical setting, retinal surgeons determine the use of preoperative IVI based on individual criteria. In this study, we investigated factors related to the potential bias of retinal surgeons in using IVI prior to vitrectomy for PDR-related complications, and evaluated the real-world outcomes of surgeon-determined preoperative IVI. Methods Medical records of 409 eyes of 409 patients who underwent 25-gauge vitrectomy for PDR complications at seven Japanese centers (22 surgeons) were retrospectively reviewed. Ocular factors, demographic and general clinical factors, surgical procedures, and postoperative complications were compared between IVI group (patients who received preoperative IVI; 87 eyes, 21.3%) and non-IVI group (patients who did not receive preoperative IVI; 322 eyes, 78.7%). In addition, baseline HbA1c in IVI group and non-IVI group was compared between eyes with and without postoperative complications. Results At baseline, IVI group was younger (P<0.001), had shorter duration of diabetes treatment (P = 0.045), and higher frequencies of neovascular glaucoma [NVG] (P<0.001) and tractional retinal detachment [TRD] (P<0.001) compared to non-IVI group. Although IVI group had higher frequencies of intraoperative retinal break and tamponade procedure, there were no significant differences in postoperative complications and additional treatments between two groups. Baseline HbA1c levels were also not correlated with postoperative complications of VH, NVG, and RD both in IVI group and non-IVI group. Logistic regression analysis identified age (P<0.001, odds ratio [OR] 0.95), presence of NVG (P<0.001, OR 20.2), and presence of TRD (P = 0.0014, OR 2.44) as preoperative factors in favor of IVI. Conclusions In this multicenter real-world clinical study, younger age and presence of NVG and TRD were identified as potential biases in using IVI before vitrectomy for PDR complications. Eyes that received preoperative IVI had more intraoperative retinal breaks requiring tamponade than eyes not receiving IVI, but postoperative outcome was not different between the two groups.

CLINICAL EFFECTIVENESS OF FIXED DOSE COMBINATION OF EMPAGLIFLOZIN AND LINAGLIPTIN (EMPA/LINA) IN PATIENTS WITH TYPE 2 DIABETES MELLITUS UNWILLING TO CONTINUE BASAL INSULIN THERAPY: A REAL-WORLD EXPERIENCE IN INDIAN SETTING

Many T2DM patients are reluctant to continue injectable insulin therapy affecting medication adherence. The objective was to investigate the clinical effectiveness with empagliozin/linagliptin (EMPA/LINA) combination in patients unwilling to continue insulin therapy. In this retrospective assessment, a total of 60 patients [(41 men, 19 women); age (± S.D.) 53.38 ± 8.49 years and disease duration 5.67±1.89 years; baseline HbA1c: 7.1±0.58%; BMI: 28.25±4.07 kg/m2 were initiated with EMPA/LINA (25/5 mg) after thorough assessment. During 12-week period, there was modest improvements in glycemic prole [baseline vs. endpoint; HbA1c: 7.1±0.58% versus 7.1±0.55% (p < 0.63), FPG 129±14 mg/dl versus 125±9.3 mg/dl, PPG 154±18 mg/dl versus 143±11 mg/dl (p=0.01), proportion of patients achieving A1C goal with no major hypoglycemia was improved from 37% to 81.48%. The incidence of overall hypoglycemia was reduced. These ndings suggest that patients with stable glycemic status reluctant to continue insulin may have effective transition to EMPA/LINA therapy

Inequalities in Glycemic Control in Youth with Type 1 Diabetes Over Time: Intersectionality Between Socioeconomic Position and Race and Ethnicity

Background Racial/ethnic health inequities have been well-documented among youth and young adults with type 1 diabetes (T1D), yet little is known about how socioeconomic position (SEP) intersects with the risk marker of race/ethnicity to predict inequities in longitudinal glycemic control. Purpose To identify patterns of SEP, race/ethnicity, and clinical characteristics that differentiate hemoglobin A1c (HbA1c) trajectories among youth and young adults after T1D diagnosis. Methods The SEARCH for Diabetes in Youth cohort includes youth with diabetes diagnosed from 2002 to 2006 and 2008 who were followed through 2015. We analyzed data from 1,313 youth and young adults with T1D with ≥3 HbA1c measures. Classification tree analysis identified patterns of baseline demographic, SEP, and clinical characteristic that best predicted HbA1c trajectories over an average of 8.3 years using group-based trajectory modeling. Results Two HbA1c trajectories were identified: Trajectory 1 (77%) with lower baseline HbA1c and mild increases (from mean 7.4% to 8.4%) and Trajectory 2 (23%) with higher baseline HbA1c and major increases (from 8.5% to 11.2%). Race/ethnicity intersected with different SEP characteristics among non-Hispanic white (NHW) than in non-whites. Public health insurance predicted high-risk Trajectory 2 membership in non-whites, whereas parental education, household structure, diagnosis age and glucose checking frequency predicted membership for NHW youth and young adults. Two characteristics, race/ethnicity and parental education alone identified 80% of the Trajectory 2 members. Conclusions Race/ethnicity intersects with multiple SEP and clinical characteristics among youth and young adults with T1D, which is associated with particularly high risk of poor long-term glycemic control.

Rationality, Efficacy, Tolerability of Empagliflozin plus Linagliptin Combination for the Management of Type 2 Diabetes Mellitus: A Systematic review of randomized controlled trials and observational studies.

Background: Treatment of diabetes mellitus includes more than one drug of different groups, which may lead to high pill burden and non-adherence to drugs. We have aimed to systematically analyze the clinical efficacy, safety and pharmacoeconomic cost-effectiveness of the fixed-dose combination of empagliflozin plus a linagliptin in Type-2 Diabetes mellitus (T2DM) patients. Methods: A literature search of PubMed/MEDLINE, SCOPUS, Google Scholar and EMBASE was performed using the MeSH terms and/or keywords“((Single-pill combination) OR ((Fixed-dose combination) OR (Combination therapy)) AND (Empagliflozin add on-to Linagliptin) OR (Empagliflozin combined with Linagliptin) OR ((Combination of Empagliflozin and Linagliptin)” from the inception to February2021. Results: Search results were found a total of 13 clinical studies. After removing duplicates and studies not according to inclusion criteria a total of eight clinical studies (Randomized controlled trials: 7; Observational cohort studies: 1) were included (n=7491). A significant reduction in the primary endpoint, the mean changes in baseline HbA1c at the end of 24 weeks and/or 52 weeks of the was found in the empagliflozin plus a linagliptin combination group in all included studies. In addition, significant efficacy was seen in decreasing the secondary endpoints such as, the mean change in the fasting plasma glucose, systolic and diastolic blood pressure (DBP) and body weight with less number of adverse events than the adverse effects with either drug alone. Conclusion: After reviewing findings from the available clinical studies of the combination of empagliflozin plus linagliptin we conclude that, the combination is effective, safe, tolerable and rationale cost effective combination compared to placebo and either drug alone for the management of T2DM in patients with inadequate glycemic control with metformin alone, patients with intoleratance to metformin, increased baseline HbA1c, patients with overweight or obesity and diabetic hypertensive, CHF, atherosclerotic cardiovascular disease and renal dysfunction patients. We suggest for more number of future randomized controlled studies in more number of T2DM patients with or without CHF and renal failure patients.