The huge prevalence of type 2 diabetes is a leading human and economic concern worldwide. The diagnosis code of type 2 diabetes includes multiple clinical phenotypes showing different degrees of ...obesity, fat distribution patterns, types of dyslipidemia, and characteristics of insulin resistance syndrome. In addition, subjects with type 2 diabetes could develop different clinical trajectories, with age being a critical factor in progression. The chronic complications of type 2 diabetes are a major cause of mortality and disability, and are ranked in the top places in western countries’ scores. The pathophysiological heterogeneity of type 2 diabetes is not captured by the current classifications and guidelines. The potential for diabetes progression and complications developing is different depending on the type 2 diabetes cluster, which is mostly regardless of the degree of glycemic control. However, the impact on quality and life expectancy with the current therapeutic approach is not always the same for every individual. Clinical research is the key to reducing the burden of diabetes. New basic, digital, and clinical approaches are obtaining useful knowledge and designing more individualized interventions to prevent, track, and treat diabetic complications. This Special Issue is a clear reflection of this methodological evolution.
Laboratory measured glycated haemoglobin (HbA1c) is the gold standard for assessing glycaemic control in people with diabetes and correlates with their risk of long‐term complications. The emergence ...of continuous glucose monitoring (CGM) has highlighted limitations of HbA1c testing. HbA1c can only be reviewed infrequently and can mask the risk of hypoglycaemia or extreme glucose fluctuations. While CGM provides insights in to the risk of hypoglycaemia as well as daily fluctuations of glucose, it can also be used to calculate an estimated HbA1c that has been used as a substitute for laboratory HbA1c. However, it is evident that estimated HbA1c and HbA1c values can differ widely. The glucose management indicator (GMI), calculated exclusively from CGM data, has been proposed. It uses the same scale (% or mmol/mol) as HbA1c, but is based on short‐term average glucose values, rather than long‐term glucose exposure. HbA1c and GMI values differ in up to 81% of individuals by more than ±0.1% and by more than ±0.3% in 51% of cases. Here, we review the factors that define these differences, such as the time period being assessed, the variation in glycation rates and factors such as anaemia and haemoglobinopathies. Recognizing and understanding the factors that cause differences between HbA1c and GMI is an important clinical skill. In circumstances when HbA1c is elevated above GMI, further attempts at intensification of therapy based solely on the HbA1c value may increase the risk of hypoglycaemia. The observed difference between GMI and HbA1c also informs the important question about the predictive ability of GMI regarding long‐term complications.
•GLP-1RAs and SGLT2i are changing the expectations of cardiovascular protection in T2D treatment.•These drugs are intended to be massively used worldwide.•However, throughout the preclinical ...programs, some possible safety concerns have arisen.•To address their actual dimension and plausibility is a worthwhile goal.•Initial inconclusive results should not discourage researchers and clinicians from this aim.
Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy ...will require advancement to injectable therapy using either a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real‐world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed‐ratio combinations (FRCs) of basal insulin and GLP‐1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta‐analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head‐to‐head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP‐1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP‐1 RAs as an alternative treatment option.
To investigate the efficacy and safety of liraglutide added to capped insulin doses in subjects with type 1 diabetes.
A 26-week, placebo-controlled, double-blind, parallel-group trial enrolling 835 ...subjects randomized 3:1 receiving once-daily subcutaneous liraglutide (1.8, 1.2, and 0.6 mg) or placebo added to an individually capped total daily dose of insulin.
Mean baseline glycated hemoglobin (HbA1c) (8.1% 65.0 mmol/mol) was significantly decreased with liraglutide versus placebo at week 26 (1.8 mg: -0.33% 3.6 mmol/mol; 1.2 mg: -0.22% 2.4 mmol/mol; 0.6 mg: -0.23% 2.5 mmol/mol; placebo: 0.01% 0.1 mmol/mol). Liraglutide significantly reduced mean body weight (-5.1, -4.0, and -2.5 kg for 1.8, 1.2, and 0.6 mg, respectively) versus placebo (-0.2 kg). Significant reductions in daily insulin dose and increases in quality of life were seen with liraglutide versus placebo. There were higher rates of symptomatic hypoglycemia (21.3 vs. 16.6 events/patient/year; P = 0.03) with liraglutide 1.2 mg vs. placebo and of hyperglycemia with ketosis >1.5 mmol/L with liraglutide 1.8 mg vs. placebo (0.5 vs. 0.1 events/patient/year; P = 0.01).
In a broad population of subjects with long-standing type 1 diabetes, liraglutide added to capped insulin reduced HbA1c, body weight, and insulin requirements but with higher rates of hypoglycemia for liraglutide 1.2 mg and hyperglycemia with ketosis for liraglutide 1.8 mg.
Background: COVID-19 entails a higher rate of complications in subjects with type 2 diabetes mellitus (T2DM). Likewise, COVID-19 infection can cause alterations in glucose metabolism that may lead to ...worse control. The aim of the study was to analyse the perceptions of a large group of Spanish physicians about the relationship between COVID-19 and T2DM, as well as the management, monitoring, and treatment of both diseases. Methods: A cross-sectional multicenter national project was conducted based on a survey which included opinion, attitude, and behavior (OAB) questions. Physicians specialised in internal medicine or endocrinology, whose usual clinical practices included the management of T2DM, responded to the survey between March and April 2021. Results: A total of 112 participants responded to the survey, from which 64.3% believed that COVID-19 entailed a higher risk of glycaemic decompensation irrespective of the presence of previously known T2DM. Obesity was considered a risk factor for poor control of T2DM by 57.7% and for a worse course of COVID-19 by 61.0%. Treatment intensification in not-on-target patients was considered by 57.1% in the presence of COVID-19 and by 73.2% in the absence of COVID-19. No participants considered the suspension of dipeptidyl peptidase 4 inhibitors (DPP-4i) in ambulatory patients, 85.7% declared that this therapeutic approach in hospitalized patients should be kept, and 88.4% supported the option of maintaining DPP-4i when corticosteroids were prescribed. Conclusion: The physicians involved in the management of T2DM and COVID-19 are aware of the bidirectional relationship between both conditions. However, the monitoring and therapeutic management of patients with T2DM who are infected by SARS-CoV-2 needs improvement through the following of the current recommendations and available evidence.
Aim
To investigate the effectiveness of premixed insulin for achieving glycaemic outcomes in clinical practice in the UK.
Materials and Methods
Electronic medical record data from The Health ...Improvement Network database were captured for adults with type 2 diabetes (T2D) uncontrolled (HbA1c ≥9%) on two or more oral antihyperglycaemic drugs (OADs) initiating premixed insulin. Effectiveness of premixed insulin was assessed by the probability and incidence of achieving glycaemic outcomes (target HbA1c <7.5% <58 mmol/mol and a ≥1% or ≥2% HbA1c reduction) over 24 months.
Results
Data from 974 participants (mean age 62 years; 56% male; 52% obese or extremely obese; mean HbA1c 11.3% 100 mmol/mol; hypertension 64%, dyslipidaemia 23% and nephropathy 21%) were analysed. The probability of achieving HbA1c <7.5% was highest during months 3‐6 (18.2%), while the cumulative probability of achieving this target plateaued between months 15‐24 (15.7%‐16.0%). Incidence of achieving all glycaemic outcomes plateaued after 12 months and differed by baseline HbA1c, but not OAD use. Factors affecting some glycaemic outcomes included a body mass index >40 kg/m2 and co‐morbidities including nephropathy and stroke.
Conclusions
In people with uncontrolled T2D (HbA1c ≥9%), glycaemic outcome achievement on premixed insulin was low at 6 months with little additional clinical benefit beyond 12 months, suggesting a high unmet need for early, timely treatment changes with more effective, simpler therapies.
Type 2 diabetes mellitus (T2DM) has become one of the leading causes of morbidity and mortality in developed countries. Low efficacy, weight gain, and hypoglycemia are the main pitfalls of previous ...treatments for T2DM. New therapies have been designed with the aim of improving the results in efficacy and quality of life. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) increase glucose-dependent insulin secretion, decrease gastric emptying, and reduce postprandial glucagon secretion. The last GLP-1 RA approved by the US Food and Drug Administration and European Medicines Agency was semaglutide. This review describes its pharmacology, core clinical data coming from the randomized controlled trials included in the development program, proven cardiovascular benefits, safety issues, and precautions for the use of semaglutide in special populations. Additionally, an overview of the positioning of semaglutide in T2DM therapy and practical issues regarding semaglutide initiation are offered.
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