Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

American Association of Clinical Endocrinology Consensus Statement: Comprehensive Type 2 Diabetes Management Algorithm - 2023 Update.

OBJECTIVE: This consensus statement provides (1) visual guidance in concise graphic algorithms to assist with clinical decision-making of health care professionals in the management of persons with type 2 diabetes mellitus to improve patient care and (2) a summary of details to support the visual guidance found in each algorithm. METHODS: The American Association of Clinical Endocrinology (AACE) selected a task force of medical experts who updated the 2020 AACE Comprehensive Type 2 Diabetes Management Algorithm based on the 2022 AACE Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan and consensus of task force authors. RESULTS: This algorithm for management of persons with type 2 diabetes includes 11 distinct sections: (1) Principles for the Management of Type 2 Diabetes; (2) Complications-Centric Model for the Care of Persons with Overweight/Obesity; (3) Prediabetes Algorithm; (4) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Dyslipidemia; (5) Atherosclerotic Cardiovascular Disease Risk Reduction Algorithm: Hypertension; (6) Complications-Centric Algorithm for Glycemic Control; (7) Glucose-Centric Algorithm for Glycemic Control; (8) Algorithm for Adding/Intensifying Insulin; (9) Profiles of Antihyperglycemic Medications; (10) Profiles of Weight-Loss Medications (new); and (11) Vaccine Recommendations for Persons with Diabetes Mellitus (new), which summarizes recommendations from the Advisory Committee on Immunization Practices of the U.S. Centers for Disease Control and Prevention. CONCLUSIONS: Aligning with the 2022 AACE diabetes guideline update, this 2023 diabetes algorithm update emphasizes lifestyle modification and treatment of overweight/obesity as key pillars in the management of prediabetes and diabetes mellitus and highlights the importance of appropriate management of atherosclerotic risk factors of dyslipidemia and hypertension. One notable new theme is an emphasis on a complication-centric approach, beyond glucose levels, to frame decisions regarding first-line pharmacologic choices for the treatment of persons with diabetes. The algorithm also includes access/cost of medications as factors related to health equity to consider in clinical decision-making.

L-Methylfolate in Diabetic Peripheral Neuropathy: A Narrative Review.

OBJECTIVE: One of the most frequently occurring complications of diabetes mellitus is peripheral neuropathy. Despite the painful symptoms associated with diabetic peripheral neuropathy (DPN), the current treatment landscape focuses on managing symptoms without addressing the underlying causes of DPN. This narrative review describes the mechanistic effects and clinical trial data supporting the use of L-methylfolate calcium (LMF), the bioactive form of folate, which is available in the United States as a prescription medical food that also contains other B vitamins for the dietary management of DPN. METHODS: Preclinical and clinical trial data evaluating the impact of LMF on DPN were identified using PubMed searches for articles published between 2010 and 2023. Search terms included: folate, LMF, diabetes, neuropathy, and neuropathic pain. Additionally, a literature search was conducted to identify studies related to LMF, genetic polymorphisms, and DPN pathophysiology. RESULTS: Several studies show that the C677T variant of the methylenetetrahydrofolate reductase gene is linked to greater risk of DPN than other methylenetetrahydrofolate reductase variants due to its inhibitory effects on several folic acid metabolic pathways. One double-blind, randomized controlled trial, 5 open-label studies, and 1 retrospective study found that LMF has a significant beneficial effect on DPN that extends beyond symptomatic relief to include modulating the underlying pathophysiology that leads to the progression and symptoms of DPN. LMF also significantly improves patient quality of life, with minimal adverse effects. CONCLUSION: Preclinical and clinical studies have found that LMF can be used to treat the underlying causes of DPN and provide long-lasting symptomatic relief.

The syndromic triad of COVID-19, type 2 diabetes, and malnutrition.

The coronavirus disease 2019 (COVID-19) pandemic challenges our collective understanding of transmission, prevention, complications, and clinical management of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Risk factors for severe infection, morbidity, and mortality are associated with age, environment, socioeconomic status, comorbidities, and interventional timing. Clinical investigations report an intriguing association of COVID-19 with diabetes mellitus and malnutrition but incompletely describe the triphasic relationship, its mechanistic pathways, and potential therapeutic approaches to address each malady and their underlying metabolic disorders. This narrative review highlights common chronic disease states that interact epidemiologically and mechanistically with the COVID-19 to create a syndromic phenotype-the COVID-Related Cardiometabolic Syndrome-linking cardiometabolic-based chronic disease drivers with pre-, acute, and chronic/post-COVID-19 disease stages. Since the association of nutritional disorders with COVID-19 and cardiometabolic risk factors is well established, a syndromic triad of COVID-19, type 2 diabetes, and malnutrition is hypothesized that can direct, inform, and optimize care. In this review, each of the three edges of this network is uniquely summarized, nutritional therapies discussed, and a structure for early preventive care proposed. Concerted efforts to identify malnutrition in patients with COVID-19 and elevated metabolic risks are needed and can be followed by improved dietary management while simultaneously addressing dysglycemia-based chronic disease and malnutrition-based chronic disease.

POINT: Artificial Sweeteners and Obesity-Not the Solution and Potentially a Problem.

OBJECTIVE: Nonnutritive sweeteners (NNS) have been widely implemented as replacements for naturally occurring sugars in a wide array of foods, beverages, and non-consumables for the sake of reducing calories. The use of these products, whether naturally occurring or manufactured, have become commonplace and accepted as de facto beneficial. This point argues that rigorous analysis of the available data do not confirm benefit and indeed suggest harm. METHODS: A literature review was conducted on all the available NNS supplements that are commonly used in all types of products. There was a focus on studies that evaluated the long-term as well as neurohormonal effects of NNS products. Key words used in the search included artificial sweeteners, nonnutritive sweeteners, saccharin, aspartame, acesulfame, sucralose, stevia, xylitol, and erythritol. RESULTS: There was a consistent trend of no to minimal benefit when NNS were used instead of calorie-containing sweeteners particularly in persons with obesity or pre-diabetes risks. There was a consistent finding of detriment to the neurohormonal regulation of satiety, weight, and energy regulation. The only studies that were neutral to positive were biased studies funded by the large food and beverage corporations or done in healthy weight individuals without any underlying health concerns and for a very short time frame. CONCLUSION: Although NNS usage has become ubiquitous, there has been very little in the way of rigorous review of the neurohormonal and physiologic effects. The arguments for NNS are purely thermodynamic in nature despite the overwhelming evidence that obesity and adiposity-related diseases are not that simplistic in their pathophysiology. Given that there are differences in how individuals process nutrition signals, very few studies focus on gender or disease predisposition differences and how they affect the outcomes when NNS are used. Studies that controlled these variables showed worsening outcomes when NNS products are used in the fight against adiposity-related diseases, such as hypertension, dyslipidemia, and diabetes. Alterations in the gut microbiome towards a more inflammatory pattern of gut microbiota is a disturbing finding in acute as well as chronic users of NNS regardless of baseline weight or disease. Most importantly, there were numerous studies that found long-term damage to the neurohormonal control of satiety in chronic users of NNS. In the fight against obesity and adiposity-related diseases, we cannot afford to blindly accept their usage based on a broken paradigm of thermodynamics and false assumptions that we are all created equal biologically.

Optimal Early Diagnosis and Monitoring of Diabetic Kidney Disease in Type 2 Diabetes Mellitus: Addressing the Barriers to Albuminuria Testing.

Chronic kidney disease (CKD) in patients with type 2 diabetes (T2D) is associated with increased risk of end-stage renal disease (ESRD) and cardiovascular disease (CVD). Urine albumin-to-creatinine ratio (UACR) is a sensitive and early indicator of kidney damage, which should be used routinely to accurately assess CKD stage and monitor kidney health. However, this test currently is performed in only a minority of patients with T2D. Here, we review the importance of albuminuria testing and current barriers that hinder patient access to UACR testing and describe solutions to such testing in a community clinical setting.

Practical Insights Into Improving Adherence to Metformin Therapy in Patients With Type 2 Diabetes.

IN BRIEF Adherence to metformin-based treatment regimens for type 2 diabetes is currently suboptimal due to a complex array of patient-, treatment-, and physician-related barriers, including physical and psychological swallowing difficulties associated with large tablets and gastrointestinal disturbances. Patients often avoid discussing these issues with their primary care providers, and delays in addressing them can lead to reduced glycemic control. This article reviews the issues commonly responsible for poor adherence to metformin and presents strategies to improve compliance, including shared decision-making and the use of different metformin formulations, including liquid metformin.

Clinical importance of achieving biochemical control with medical therapy in adult patients with acromegaly.

In acromegaly, achieving biochemical control (growth hormone [GH] level <1.0 ng/mL and age- and sex-normalized levels of insulin-like growth factor 1 [IGF-1]) through timely diagnosis and appropriate treatment provides an opportunity to improve patient outcomes. Diagnosis of acromegaly is challenging because it is rooted in observing subtle clinical manifestations, and it is typical for acromegaly to evolve for up to 10 years before it is recognized. This results in chronic exposure to elevated levels of GH and IGF-1 and delay in patients receiving appropriate treatment, which consequently increases mortality risk. In this review, the clinical impact of elevated GH and IGF-1 levels, the effectiveness of current therapies, and the potential role of novel treatments for acromegaly will be discussed. Clinical burden of acromegaly and benefits associated with management of GH and IGF-1 levels will be reviewed. Major treatment paradigms in acromegaly include surgery, medical therapy, and radiotherapy. With medical therapies, such as somatostatin analogs, dopamine agonists, and GH receptor antagonists, a substantial proportion of patients achieve reduced GH and normalized IGF-1 levels. In addition, signs and symptoms, quality of life, and comorbidities have also been reported to improve to varying degrees in patients who achieve biochemical control. Currently, there are several innovative therapies in development to improve patient outcomes, patient use, and access. Timely biochemical control of acromegaly ensures that the patient can ultimately improve morbidity and mortality from this disease and its extensive consequences.