diabetes mellitus, type 2

RPR Commentary: Continuous glucose monitoring is a tool that should be used to address specific glucose management challenges. There are significant hazards with overuse. James W. Mold, MD, MPH

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Importance Continuous glucose monitoring (CGM), initially recommended primarily for people with type 1 diabetes, has rapidly expanded to patients with type 2 diabetes and, more recently, even to individuals without diabetes. This broadening use underscores the importance of critically examining the evidence supporting CGM across populations, clarifying where benefits are established, where they are modest, and where they remain uncertain.

Observations We reviewed systematic reviews and meta-analyses of randomized trials and clinical guidelines evaluating CGM use beyond type 1 diabetes, with particular attention to glycemic outcomes, hypoglycemia, patient-reported outcomes, and potential unintended consequences in nonpregnant adults. In adults with type 2 diabetes, evidence from randomized trials consistently demonstrated that CGM use was associated, on average, with a modest yet consistent reduction in hemoglobin A1c of approximately 0.3% compared with finger-stick monitoring or usual care; some patients benefited considerably more. Only limited and indirect evidence supported the adoption of CGM in people with type 2 diabetes not receiving glucose-lowering therapy or in those with prediabetes or obesity.

Conclusions and Relevance CGM should be deployed in response to a specific patient problem rather than as a default intervention. Deliberate, equitable deployment of CGM that is aligned with patient goals, clinical context, and system capacity will be necessary to ensure that those most likely to benefit are not left behind, while avoiding overuse in populations for whom benefit remains unproven.

Author/s:

Dower, Justin A., Johansson, Minna, Camp, Anne W.

What Is Diverticulitis?

Megan George — Fri, 14 Nov 2025 19:07:17 +0000

Date Added:

November 14, 2025

Journal/Publication:

JAMA Patient Page

Publication Date:

November 13, 2025

URL:

What Is Diverticulitis?

Type:

Patient Education Materials

Format:

Poster

DOI (1):

10.1001/jama.2025.17403

Keywords

Gastroenterology

Diverticulitis

Diverticulum

PMID (1):

41231515

MeSH

diabetes mellitus, type 2

Analgesics

analgesics, opioid

Anti-Inflammatory Agents

Anti-Inflammatory Agents, Non-Steroidal

Diverticulitis

Diverticulitis, Colonic

risk factors

Diverticulum, colon

Inflammation

Ehlers-Danlos Syndrome

Information for patients about diverticulitis. James W. Mold, MD, MPH

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Diverticulitis involves inflammation of outpouchings of the intestinal wall, a condition known as diverticulosis.

Risk factors for diverticulosis include being older than 65 years, obesity (body mass index [BMI] of 30 or more), high blood pressure, type 2 diabetes, certain medications (such as opioids, steroids, and nonsteroidal anti-inflammatory drugs [NSAIDs]), connective tissue diseases (such as polycystic kidney disease, Marfan syndrome, and Ehlers-Danlos syndrome), and specific genetic variants.1

By age 60 years, nearly 60% of people have diverticulosis, most often on the left side of the colon. About 1% to 4% of people with diverticulosis develop diverticulitis in their lifetime. Acute diverticulitis affects about 180 per 100 000 people in the US each year, resulting in approximately 200 000 hospitalizations annually.

Author/s:

Shreya Narayanan, Christopher D. Jackson, MD

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Megan George — Tue, 11 Nov 2025 14:43:19 +0000

Date Added:

November 11, 2025

Journal/Publication:

JAMA

Publication Date:

November 10, 2025

URL:

Metabolic Dysfunction–Associated Steatotic Liver Disease in Adults: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.19615

Keywords

liver disease

steatotic liver disease

MASLD

Steatohepatitis

PMID (1):

41212550

MeSH

Glucagon-Like Peptide-1 Receptor Agonists

semaglutide

cardiovascular diseases

prevalence

diabetes mellitus

diabetes mellitus, type 2

Prediabetic State

liver cirrhosis

A review of metabolic dysfunction–associated steatotic liver disease in adults. James W. Mold, MD, MPH

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Importance Metabolic dysfunction–associated steatotic liver disease (MASLD) includes a range of liver conditions, progressing from isolated steatosis (characterized by fat accumulation in the liver without inflammation) to metabolic dysfunction–associated steatohepatitis (MASH), which involves fat accumulation and inflammation in the liver. The presence of MASLD is associated with increased morbidity and mortality due to liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers.

Observations The most common chronic liver disease worldwide, MASLD affects approximately 30% to 40% of the general adult population globally (with varying prevalence across continents), including approximately 60% to 70% of individuals with type 2 diabetes and approximately 70% to 80% of those with obesity. It is typically diagnosed based on an ultrasonographic finding of hepatic steatosis, along with at least 1 of 5 features of the metabolic syndrome (abdominal overweight or obesity, prediabetes or type 2 diabetes, hypertension, elevated level of plasma triglycerides, and low level of high-density lipoprotein cholesterol) for women who consume less than 140 g/wk of alcohol (<2 standard drinks/d) and for men who consume less than 210 g/wk (<3 standard drinks/d) and have no other known causes of steatosis such as use of a particular medication (eg, corticosteroids, tamoxifen, or methotrexate), hepatitis C, or iron overload. Other risk factors for MASLD include older age (≥50 years) and male sex (male:female ratio approximately 2). The Fibrosis-4 index (a scoring system incorporating age, serum levels of aspartate aminotransferase and alanine aminotransferase, and platelet count) and vibration-controlled transient elastography (a noninvasive imaging technique) are commonly used to stage hepatic fibrosis in patients with MASLD. Cardiovascular disease is the leading cause of death, followed by certain extrahepatic cancers (primarily gastrointestinal, breast, and gynecologic cancer) and liver-related complications, including cirrhosis, hepatic decompensation (ascites, hepatic encephalopathy, or variceal bleeding), and hepatocellular carcinoma. First-line treatment of MASLD involves behavioral modifications (including hypocaloric low-carbohydrate and low-fat diets, physical exercise, and avoidance of alcohol) and management of type 2 diabetes, obesity, hypertension, and hyperlipidemia. Bariatric surgery should be considered for patients with MASLD and a body mass index greater than 35. Resmetirom (a liver-directed, thyroid hormone receptor β-selective agonist) and subcutaneous semaglutide (a glucagon-like peptide-1 receptor agonist) are conditionally approved by the US Food and Drug Administration (FDA) for the treatment of adults with MASH who have moderate to advanced fibrosis.

Conclusions A highly prevalent condition among adults worldwide, MASLD is associated with liver-related complications, hepatocellular carcinoma, cardiovascular disease, and certain extrahepatic cancers. First-line treatment includes behavioral modifications, including a weight-reducing diet, physical exercise, and avoidance of alcohol. Resmetirom and semaglutide are conditionally FDA-approved medications for the treatment of adults with MASH and moderate to advanced fibrosis.

Author/s:

Herbert Tilg, Salvatore Petta, Norbert Stefan, Giovanni Targher

Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Megan George — Tue, 16 Sep 2025 13:46:37 +0000

Date Added:

September 16, 2025

Journal/Publication:

JAMA Pediatrics

Publication Date:

September 15, 2025

URL:

Efficacy and Safety of GLP-1 RAs in Children and Adolescents With Obesity or Type 2 Diabetes: A Systematic Review and Meta-Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamapediatrics.2025.3243

Keywords

diabetes

Diabetes and Endocrinology

PMID (1):

40952752

MeSH

diabetes mellitus, type 2

Glycated Hemoglobin

overweight

Glucagon-Like Peptide-1 Receptor Agonists

glucagon-like peptide 1

Prediabetic State

blood pressure

pediatric obesity

Digestive System Diseases

A review of what we know about the use of GLP-1 RAs in children and adolescents. James W. Mold, MD, MPH

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Importance Obesity affects 1 in 5 children and adolescents, increasing the risk of type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are among the few pharmacotherapy options available for this population, necessitating a comprehensive evaluation of efficacy and safety.

Objective To assess the efficacy and safety of GLP-1 RAs in children and adolescents (<18 years) with obesity, prediabetes, or T2D.

Data Sources A systematic search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomized clinical trials (RCTs) published from inception until February 28, 2025. Data analysis was completed from January 2025 to April 2025.

Study Selection RCTs comparing GLP-1 RAs to placebo in children and adolescents with obesity, overweight, prediabetes, or T2D with reported safety and efficacy data were included.

Data Extraction and Synthesis Two reviewers independently extracted data on sample size, population, interventions, follow-up, and outcomes. Risk of bias was assessed using version 2 of the Cochrane risk of bias tool (RoB2). Efficacy outcomes (except lipids) were analyzed as estimated treatment differences, lipids as estimated treatment ratios, and safety via rate ratios. A random-effects inverse variance model was used for all outcomes.

Main Outcomes and Measures The primary efficacy outcomes were change in hemoglobin A1c (HbA1c) (in percentage points), fasting glucose (in milligrams per deciliter), body weight (in kilograms), body mass index (BMI, calculated as weight in kilograms divided by height in meters squared), BMI z scores or percentiles, BMI standard deviation score (SDS), lipid outcomes, and blood pressure. Exploratory efficacy outcomes included obstructive sleep apnea and metabolic dysfunction–associated steatohepatitis or metabolic dysfunction–associated steatotic liver disease. Safety outcomes included gastrointestinal adverse effects (GI AEs), infections, hepatobiliary disorders, suicidal ideation or behaviors, depression, hypoglycemia, and adverse event discontinuations.

Results A total of 18 RCTs (11 in obesity, 6 in T2D, and 1 in prediabetes) with 1402 participants (838 GLP-1 RA users and 564 placebo) were included (mean [range] age, 13.7 [6-17] years; 831 female participants (59.3%); median [IQR] treatment duration, 0.51 [0.25-1.00] years). GLP-1 RAs significantly reduced HbA1c (−0.44%; 95% CI, −0.68% to −0.21%), fasting glucose (−9.92 mg/dL; 95% CI, −16.20 to −3.64), body weight (−3.02 kg; 95% CI, −4.98 to −1.06), BMI (−1.45; 95% CI, −2.40 to −0.49), BMI SDS (−0.20; 95% CI, −0.36 to −0.05), BMI percentile (−7.24%; 95% CI, −12.97% to −1.51%), and systolic blood pressure (−2.73 mm Hg; 95% CI, −4.04 to −1.43) and increased GI AE (log[rate ratio] [RR], 0.75). Other AEs, including suicidal ideation or behaviors, showed no significant differences.

Conclusions and Relevance In this systematic review and meta-analysis of 18 trials, GLP-1 RAs significantly improved glycemic, weight, and cardiometabolic outcomes in children and adolescents with T2D or obesity. Available data over a relatively short follow-up suggested suicidal ideation or behaviors were not significantly different, although GI AEs warrant attention in long-term management.

Author/s:

Pareeta Kotecha, Wenxi Huang, Ya-Yun Yeh

Managing Adverse Effects of Incretin-Based Medications for Obesity

Megan George — Fri, 01 Aug 2025 13:22:15 +0000

Date Added:

August 1, 2025

Journal/Publication:

JAMA Insights

Publication Date:

July 29, 2025

URL:

Managing Adverse Effects of Incretin-Based Medications for Obesity

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.11153

Keywords

Cardiovascular Diseases

overweight

PMID (1):

40728833

MeSH

diabetes mellitus, type 2

Glucagon-Like Peptide-1 Receptor Agonists

cardiovascular diseases

overweight

Gastric Inhibitory Polypeptide

renal insufficiency

Information on how to deal with the side effects of obesity medications. James W. Mold, MD, MPH

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This JAMA Insights explores optimal strategies for managing the adverse effects associated with incretin-based medications for obesity, including semaglutide and tirzepatide.

Author/s:

Robert F Kushner, Jaime P Almandoz, Domenica M Rubino

Obesity in Adolescents: A Review

Alex Haga — Sat, 10 Aug 2024 18:21:58 +0000

Date Added:

August 10, 2024

Journal/Publication:

JAMA

Publication Date:

August 5, 2024

URL:

Obesity in Adolescents: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.11809

Keywords

PMID (1):

39102244

MeSH

cardiovascular diseases

diabetes mellitus

diabetes mellitus, type 2

depression

Life Style

exercise

A review of obesity management in adolescents. James W. Mold, MD, MPH

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Importance: Obesity affects approximately 21% of US adolescents and is associated with insulin resistance, hypertension, dyslipidemia, sleep disorders, depression, and musculoskeletal problems. Obesity during adolescence has also been associated with an increased risk of mortality from cardiovascular disease and type 2 diabetes in adulthood.

Observations: Obesity in adolescents aged 12 to younger than 18 years is commonly defined as a body mass index (BMI) at the 95th or greater age- and sex-adjusted percentile. Comprehensive treatment in adolescents includes lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Lifestyle modification therapy, which includes dietary, physical activity, and behavioral counseling, is first-line treatment; as monotherapy, lifestyle modification requires more than 26 contact hours over 1 year to elicit approximately 3% mean BMI reduction. Newer antiobesity medications, such as liraglutide, semaglutide, and phentermine/topiramate, in combination with lifestyle modification therapy, can reduce mean BMI by approximately 5% to 17% at 1 year of treatment. Adverse effects vary, but severe adverse events from these newer antiobesity medications are rare. Surgery (Roux-en-Y gastric bypass and vertical sleeve gastrectomy) for severe adolescent obesity (BMI ≥120% of the 95th percentile) reduces mean BMI by approximately 30% at 1 year. Minor and major perioperative complications, such as reoperation and hospital readmission for dehydration, are experienced by approximately 15% and 8% of patients, respectively. Determining the long-term durability of all obesity treatments warrants future research.

Conclusions and relevance: The prevalence of adolescent obesity is approximately 21% in the US. Treatment options for adolescents with obesity include lifestyle modification therapy, pharmacotherapy, and metabolic and bariatric surgery. Intensive lifestyle modification therapy reduces BMI by approximately 3% while pharmacotherapy added to lifestyle modification therapy can attain BMI reductions ranging from 5% to 17%. Surgery is the most effective intervention for adolescents with severe obesity and has been shown to achieve BMI reduction of approximately 30%.

Author/s:

Aaron S Kelly, Sarah C Armstrong, Marc P Michalsky, Claudia K Fox

Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis

Alex Haga — Sun, 16 Jun 2024 19:07:38 +0000

Date Added:

June 16, 2024

Journal/Publication:

Circulation

Publication Date:

June 4, 2024

Issue:

Volume:

149

Pages:

1789–1801

URL:

Sodium-Glucose Cotransporter-2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1161/CIRCULATIONAHA.124.069568

Keywords

heart failure

metabolic syndrome

Renal Insufficiency

sodium-glucose cotransporter-2 inhibitors

PMID (1):

PMC11149938

MeSH

Cardiovascular Diseases* / mortality

diabetes mellitus

Type 2 / complications

diabetes mellitus, type 2

Type 2 / mortality

renal insufficiency

Chronic / drug therapy

Chronic / mortality

Sodium-Glucose Transporter 2 Inhibitors* / adverse effects

Sodium-Glucose Transporter 2 Inhibitors* / therapeutic use

SGLT2 inhibitors reduce the risk of death and hospitalization from CHF probably because of their osmotic diuretic effect. They have not been compared to other less expensive diuretics to my knowledge. James W. Mold, MD, MPH

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Background: Sodium-glucose cotransporter-2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear.

Methods: This was a collaborative trial-level meta-analysis from the SGLT2i Meta-analysis Cardio-Renal Trialists Consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across 3 patient populations (patients with diabetes at high risk for atherosclerotic cardiovascular disease, heart failure [HF], or chronic kidney disease). The outcomes of interest were MACE (composite of cardiovascular death, myocardial infarction , or stroke), individual components of MACE (inclusive of fatal and nonfatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i versus placebo were meta-analyzed across trials and examined across key subgroups (established atherosclerotic cardiovascular disease, previous myocardial infarction, diabetes, previous HF, albuminuria, chronic kidney disease stages, and risk groups).

Results: A total of 78 607 patients across 11 trials were included: 42 568 (54.2%), 20 725 (26.4%), and 15 314 (19.5%) were included from trials of patients with diabetes at high risk for atherosclerotic cardiovascular disease, HF, or chronic kidney disease, respectively. SGLT2i reduced the rate of MACE by 9% (hazard ration [HR], 0.91 [95% CI, 0.87-0.96], P<0.0001) with a consistent effect across all 3 patient populations (I2=0%) and across all key subgroups. This effect was primarily driven by a reduction in cardiovascular death (HR, 0.86 [95% CI, 0.81-0.92], P<0.0001), with no significant effect for myocardial infarction in the overall population (HR, 0.95 [95% CI, 0.87-1.04], P=0.29), and no effect on stroke (HR, 0.99 [95% CI, 0.91-1.07], P=0.77). The benefit for cardiovascular death was driven primarily by reductions in HF death and sudden cardiac death (HR, 0.68 [95% CI, 0.46-1.02] and HR, 0.86 [95% CI, 0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (Pinteraction=0.02).

Conclusions: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of atherosclerotic cardiovascular disease, diabetes, kidney function, or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of cardiovascular death, particularly HF death and sudden cardiac death, without a significant effect on myocardial infarction in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.

Keywords: diabetes mellitus; heart failure; meta-analysis; metabolic syndrome; renal insufficiency, chronic; sodium-glucose cotransporter-2 inhibitors.

Author/s:

Siddharth M Patel, Yu Mi Kang, KyungAh Im, Brendon L Neuen, Stefan D Anker, Deepak L Bhatt, Javed Butler, David Z I Cherney

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Erin Blanchette — Tue, 26 Mar 2024 16:29:29 +0000

Date Added:

March 26, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 14, 2024

URL:

Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.1137

Keywords

diabetes

Diabetes and Endocrinology

Endocrinology

insulin

PMID (1):

38483370

MeSH

diabetes mellitus

diabetes mellitus, type 2

dipeptidyl-peptidase IV inhibitors

diabetes mellitus, type 1

blood glucose

Hypoglycemia

Insulins

Guidance for management of diabetes in patients at risk of hypoglycemia. James W. Mold, MD, MPH

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More than 30 million people in the US have diabetes, approximately 5% with type 1 and approximately 95% with type 2. About 5 million individuals in the US with type 2 diabetes use insulin and 7 million take sulfonylureas; both of these medications have a greater association with hypoglycemia than metformin, glucagon-like peptide 1 receptor agonists, dipeptidyl peptidase 4 inhibitors, or sodium-glucose cotransporter 2 inhibitors. Each month, 70% of people with type 1 diabetes experience some degree of hypoglycemia.1 Level 1 hypoglycemia is defined as blood glucose of 54 to 70 mg/dL; level 2 is less than 54 mg/dL; and severe hypoglycemia (level 3) occurs when low blood glucose levels cause neurologic or physical symptoms that require help from others. Furthermore, recurrent severe hypoglycemia increases risk of future dementia.2 Hypoglycemia occurs more often in people with lower education, lower income, and food insecurity.3 This synopsis focuses on outpatient management of diabetes with high risk of hypoglycemia; the guideline also addresses prevention of hypoglycemia in hospitalized patients.4

Author/s:

Celeste C Thomas, Karishma Chopra, Andrew M Davis

What Should I Know About Injectable Weight-Loss Medications?

Erin Blanchette — Tue, 19 Mar 2024 17:42:08 +0000

Date Added:

March 19, 2024

Journal/Publication:

JAMA Internal Medicine

Publisher:

American Medical Association

Publication Date:

March 11, 2024

URL:

What Should I Know About Injectable Weight-Loss Medications?

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jamainternmed.2023.7268

Keywords

Feeding and Eating Disorders

PMID (1):

38466303

MeSH

Liraglutide

diabetes mellitus

diabetes mellitus, type 2

Information for patients regarding injectable medications for weight loss. James W. Mold, MD, MPH

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How Do I Know If Injectable Weight-Loss Medications Are Right for Me?

The decision to start an injectable weight-loss medication is based on several factors. These include weight, medical history, personal preference, and medication cost. Talk with your health care professional about whether these medications are right for you.

Author/s:

Andrew Kraftson, Dina Griauzde

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes The GRADE Randomized Clinical Trial

Aubrey Delammermore — Sat, 27 May 2023 05:00:00 +0000

Date Added:

May 27, 2023

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

May 22, 2023

Pages:

E1-E10

URL:

Comparative Effects of Glucose-Lowering Medications on Kidney Outcomes in Type 2 Diabetes The GRADE Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jamainternmed.2023.1487

Keywords

Intention to Treat Analysis

PMID (1):

37213109

MeSH

Disease Progression

Kidney Diseases

renal dialysis

diabetes mellitus, type 2

glucose

In patients with T2DM, if your objective is to protect the kidneys, there is no need to switch to newer, more expensive meds. James W. Mold, MD, MPH.

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Importance: Type 2 diabetes (T2D) is the leading cause of kidney disease in the US. It is not known whether glucose-lowering medications differentially affect kidney function.

Objective: To evaluate kidney outcomes in the Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness (GRADE) trial comparing 4 classes of glucose-lowering medications added to metformin for glycemic management in individuals with T2D.

Design, setting, and participants: A randomized clinical trial was conducted at 36 sites across the US. Participants included adults with T2D for less than 10 years, a hemoglobin A1c level between 6.8% and 8.5%, and estimated glomerular filtration rate (eGFR) greater than or equal to 60 mL/min/1.73 m2 who were receiving metformin treatment. A total of 5047 participants were enrolled between July 8, 2013, and August 11, 2017, and followed up for a mean of 5.0 years (range, 0-7.6 years). Data were analyzed from February 21, 2022, to March 27, 2023.

Interventions: Addition of insulin glargine, glimepiride, liraglutide, or sitagliptin to metformin, with the medication combination continued until the HbA1c was greater than 7.5%; thereafter, insulin was added to maintain glycemic control.

Main outcomes and measures: Chronic eGFR slope (change in eGFR between year 1 and trial end) and a composite kidney disease progression outcome (albuminuria, dialysis, transplant, or death due to kidney disease). Secondary outcomes included incident eGFR less than 60 mL/min/1.73 m2, 40% decrease in eGFR to less than 60 mL/min/1.73 m2, doubling of urine albumin-to-creatinine ratio (UACR) to 30 mg/g or greater, and progression of Kidney Disease Improving Global Outcomes stage. Analyses were intention-to-treat.

Results: Of the 5047 participants, 3210 (63.6%) were men. Baseline characteristics were mean (SD) age 57.2 (10.0) years; HbA1c 7.5% (0.5%); diabetes duration, 4.2 (2.7) years; body mass index, 34.3 (6.8); blood pressure 128.3/77.3 (14.7/9.9) mm Hg; eGFR 94.9 (16.8) mL/min/1.73 m2; and median UACR, 6.4 (IQR 3.1-16.9) mg/g; 2933 (58.1%) were treated with renin-angiotensin-aldosterone inhibitors. Mean chronic eGFR slope was -2.03 (95% CI, -2.20 to -1.86) mL/min/1.73 m2 per year for patients receiving sitagliptin; glimepiride, -1.92 (95% CI, -2.08 to -1.75) mL/min/1.73 m2 per year; liraglutide, -2.08 (95% CI, -2.26 to -1.90) mL/min/1.73 m2 per year; and insulin glargine, -2.02 (95% CI, -2.19 to -1.84) mL/min/1.73 m2 per year (P = .61). Mean composite kidney disease progression occurred in 135 (10.6%) patients receiving sitagliptin; glimepiride, 155 (12.4%); liraglutide, 152 (12.0%); and insulin glargine, 150 (11.9%) (P = .56). Most of the composite outcome was attributable to albuminuria progression (98.4%). There were no significant differences by treatment assignment in secondary outcomes. There were no adverse kidney events attributable to medication assignment.

Conclusions and relevance: In this randomized clinical trial, among people with T2D and predominantly free of kidney disease at baseline, no significant differences in kidney outcomes were observed during 5 years of follow-up when a dipeptidyl peptidase 4 inhibitor, sulfonylurea, glucagonlike peptide 1 receptor agonist, or basal insulin was added to metformin for glycemic control.

Author/s:

Wexler, D. J., de Boer, I. H., Ghosh, A., Younes, N., Bebu, I., Inzucchi, S. E., McGill, J. B., Mudaliar, S., Schade, D., Steffes, M., Tamborlane, W. V., Tan, M. H., Ismail-Beigi, F., GRADE Research Group

Nocturnal hypoglycemia is underdiagnosed in older people with insulin-treated type 2 diabetes: The HYPOAGE observational study

Aubrey Delammermore — Wed, 05 Apr 2023 05:00:00 +0000

Date Added:

April 5, 2023

Journal/Publication:

Journal of the American Geriatrics Society

Publisher:

Geriatric Healthcare Professionals

Publication Date:

March 25, 2023

URL:

Nocturnal hypoglycemia is underdiagnosed in older people with insulin-treated type 2 diabetes: The HYPOAGE observational study

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1111/jgs.18341

Keywords

basal insulin analogues

continuous glucose monitoring

glycemic control

Hypoglycemics

type 2 diabetes

PMID (1):

36965179

MeSH

diabetes mellitus, type 2

Glycated Hemoglobin

Blood Glucose Self-Monitoring

Geriatric Assessment

Hypoglycemia

A significant number of people with insulin-requiring diabetes over 75 years of age having nocturnal hypoglycemic episodes. The sole purpose of treatment in most patients of that age is symptom control due to osmotic diuresis, which doesn't require A1c levels of 7.5% or less. "First, do no harm." James W. Mold, MD, MPH

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Background: There is a lack of real-life data regarding the frequency and predictive factors of hypoglycemia in older patients with type 2 diabetes (T2D). This study aimed to determine the frequency and predictors of hypoglycemia in older patients with insulin-treated T2D.

Methods: This prospective multicenter study included 155 insulin-treated T2D patients aged 75 years and older with ≥2 self-monitoring of blood glucose (SMBG) daily controls. Participants underwent a geriatric and diabetic assessment and received ambulatory blinded continuous glucose monitoring (CGM) for 28 consecutive days with FreeStyle Libre Pro® sensor. Study population (n = 141) has >70% CGM active time. Multivariable logistic regressions were used to identify factors associated with SMBG confirmed hypoglycemia (≥70 mg/dL) and with nocturnal level 2 time below range (glucose concentration <54 mg/dL during ≥15 consecutive min between 0.00 and 6.00 am).

Results: The mean age of the 141 analyzed patients was 81.5 ± 5.3 years and 56.7% were male. The mean baseline HbA1c was 7.9% ± 1.0%. After geriatric assessment, 102 participants (72.3%) were considered as complex and 39 (27.7%) as healthy. The primary endpoint (confirmed SMBG <70 mg/dL) occurred in 37.6% patients. In multivariable analysis, the risk of SMBG-confirmed hypoglycemia was positively associated with a longer duration of diabetes (OR (+1 year) =1.04, (1.00-1.08), p = 0.04) and glycemic variability assessed by CGM (CV %) (OR (+1%) = 1.12, [1.05-1.19], p = <0.001). Nighty-two patients (65.2%) experienced nocturnal time in hypoglycemia (i.e., <54 mg/dL during ≥15 consecutive min between midnight and 6 a.m.). In multivariable analyses, cognitive impairment (OR: 9.31 [2.59-33.4]), heart failure (OR: 4.81 [1;48-15.6]), and depressive disorder (OR: 0.19 [0.06-0.53]) were associated with nocturnal time in hypoglycemia.

Conclusion: Nocturnal hypoglycemia is very common and largely underdiagnosed in older patients with insulin-treated T2D. CGM is a promising tool to better identify hypoglycemia and adapt diabetes management in this population.

Author/s:

Boureau, A., Guyomarch, B., Gourdy, P., Allix, I., Annweiler, C., Cervantes, N., Chapelet, G., Delabriere, I., Guyonnet, S., Litke, R., Paccalin, M., Penfornis, A., Saulnier, P., Wargny, M., Hadjadj, S., de Decker, L., Cariou, B.

Heart Failure With Preserved Ejection Fraction

Rowan Hutchins — Sun, 19 Mar 2023 05:00:00 +0000

Date Added:

March 19, 2023

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

March 14, 2023

Issue:

Volume:

329

Pages:

827-838

URL:

Heart Failure With Preserved Ejection Fraction

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2023.2020

Keywords

PMID (1):

36917048

MeSH

furosemide

Sodium Potassium Chloride Symporter Inhibitors

empagliflozin

quality of life

diabetes mellitus

diabetes mellitus, type 2

A review of the possible causes, diagnosis, and management of heart failure with preserved ejection fraction. Notice that SGLT2 inhibitors reduced hospitalizations and cardiovascular deaths by <2% (absolute risk reduction) per year and have not been compared head-to-head against less expensive meds like HCTZ or ramipril. James W. Mold, MD, MPH

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Importance Heart failure with preserved ejection fraction (HFpEF), defined as HF with an EF of 50% or higher at diagnosis, affects approximately 3 million people in the US and up to 32 million people worldwide. Patients with HFpEF are hospitalized approximately 1.4 times per year and have an annual mortality rate of approximately 15%.

Observations Risk factors for HFpEF include older age, hypertension, diabetes, dyslipidemia, and obesity. Approximately 65% of patients with HFpEF present with dyspnea and physical examination, chest radiographic, echocardiographic, or invasive hemodynamic evidence of HF with overt congestion (volume overload) at rest. Approximately 35% of patients with HFpEF present with “unexplained” dyspnea on exertion, meaning they do not have clear physical, radiographic, or echocardiographic signs of HF. These patients have elevated atrial pressures with exercise as measured with invasive hemodynamic stress testing or estimated with Doppler echocardiography stress testing. In unselected patients presenting with unexplained dyspnea, the H2FPEF score incorporating clinical (age, hypertension, obesity, atrial fibrillation status) and resting Doppler echocardiographic (estimated pulmonary artery systolic pressure or left atrial pressure) variables can assist with diagnosis (H2FPEF score range, 0-9; score >5 indicates more than 95% probability of HFpEF). Specific causes of the clinical syndrome of HF with normal EF other than HFpEF should be identified and treated, such as valvular, infiltrative, or pericardial disease. First-line pharmacologic therapy consists of sodium-glucose cotransporter type 2 inhibitors, such as dapagliflozin or empagliflozin, which reduced HF hospitalization or cardiovascular death by approximately 20% compared with placebo in randomized clinical trials. Compared with usual care, exercise training and diet-induced weight loss produced clinically meaningful increases in functional capacity and quality of life in randomized clinical trials. Diuretics (typically loop diuretics, such as furosemide or torsemide) should be prescribed to patients with overt congestion to improve symptoms. Education in HF self-care (eg, adherence to medications and dietary restrictions, monitoring of symptoms and vital signs) can help avoid HF decompensation.

Conclusions and Relevance Approximately 3 million people in the US have HFpEF. First-line therapy consists of sodium-glucose cotransporter type 2 inhibitors, exercise, HF self-care, loop diuretics as needed to maintain euvolemia, and weight loss for patients with obesity and HFpEF.

Author/s:

Redfield, Margaret, Borlaug, Barry

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Aubrey Delammermore — Thu, 23 Feb 2023 06:00:00 +0000

Date Added:

February 23, 2023

Journal/Publication:

Annals of Internal Medicine

Publisher:

American College of Physicians

Publication Date:

February 7, 2023

URL:

Vitamin D and Risk for Type 2 Diabetes in People With Prediabetes : A Systematic Review and Meta-analysis of Individual Participant Data From 3 Randomized Clinical Trials

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

0.7326/M22-3018

Keywords

Kidney

Cholecalciferol

Intention to Treat Analysis

type 2 diabetes

Randomized Controlled Trials as Topic

PMID (1):

36745886

MeSH

diabetes mellitus, type 2

In patients with prediabetes, Vitamin D supplementation appears to improve blood glucose levels and reduce progression to diabetes. James W. Mold, MD, MPH

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Background: The role of vitamin D in people who are at risk for type 2 diabetes remains unclear.

Purpose: To evaluate whether administration of vitamin D decreases risk for diabetes among people with prediabetes.

Data sources: PubMed, Embase, and ClinicalTrials.gov from database inception through 9 December 2022.

Study selection: Eligible trials that were specifically designed and conducted to test the effects of oral vitamin D versus placebo on new-onset diabetes in adults with prediabetes.

Data extraction: The primary outcome was time to event for new-onset diabetes. Secondary outcomes were regression to normal glucose regulation and adverse events. Prespecified analyses (both unadjusted and adjusted for key baseline variables) were conducted according to the intention-to-treat principle.

Data synthesis: Three randomized trials were included, which tested cholecalciferol, 20 000 IU (500 mcg) weekly; cholecalciferol, 4000 IU (100 mcg) daily; or eldecalcitol, 0.75 mcg daily, versus matching placebos. Trials were at low risk of bias. Vitamin D reduced risk for diabetes by 15% (hazard ratio, 0.85 [95% CI, 0.75 to 0.96]) in adjusted analyses, with a 3-year absolute risk reduction of 3.3% (CI, 0.6% to 6.0%). The effect of vitamin D did not differ in prespecified subgroups. Among participants assigned to the vitamin D group who maintained an intratrial mean serum 25-hydroxyvitamin D level of at least 125 nmol/L (≥50 ng/mL) compared with 50 to 74 nmol/L (20 to 29 ng/mL) during follow-up, cholecalciferol reduced risk for diabetes by 76% (hazard ratio, 0.24 [CI, 0.16 to 0.36]), with a 3-year absolute risk reduction of 18.1% (CI, 11.7% to 24.6%). Vitamin D increased the likelihood of regression to normal glucose regulation by 30% (rate ratio, 1.30 [CI, 1.16 to 1.46]). There was no evidence of difference in the rate ratios for adverse events (kidney stones: 1.17 [CI, 0.69 to 1.99]; hypercalcemia: 2.34 [CI, 0.83 to 6.66]; hypercalciuria: 1.65 [CI, 0.83 to 3.28]; death: 0.85 [CI, 0.31 to 2.36]).

Limitations: Studies of people with prediabetes do not apply to the general population. Trials may not have been powered for safety outcomes.

Conclusion: In adults with prediabetes, vitamin D was effective in decreasing risk for diabetes.

Primary funding source: None. (PROSPERO: CRD42020163522).

Author/s:

Pittas, A. G., Kawahara, T., Jorde, R., Dawson-Hughes, B., Vickery, E. M., Angellotti, E., Nelson, J., Trikalinos, T. A., Balk, E. M.

GLP1Agonists and SGLT2 Inhibitors Table

Saige Blanchard — Thu, 10 Mar 2022 06:00:00 +0000

Date Added:

March 10, 2022

Publication Date:

February 6, 2022

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Poster

MeSH

diabetes mellitus, type 2

Sodium-Glucose Transporter 2 Inhibitors

Glucagon-Like Peptide-1 Receptor

Patient Selection

This table shows the relative risk reduction (RRR) and absolute risk reduction (ARR) as percentages for GLP1 agonists and SGLT2 Inhibitors, based upon RCTs of at least one year duration. In most cases, the participants were at high risk for adverse CV events, but the ARRs were still fairly small, with insufficient information about how these drugs perform vs. other, less expensive antihyperglycemic agents. James W. Mold, MD, MPH

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Based upon the following two meta-analyses:
1. Alexander JT, et al. The longer-term benefits and harms of glucagon-like peptide-1 receptor agonists: A Systematic review and meta-analysis. JGIM, 2021; 7(2): 415-43.
2. Alexander JT, et al. Longer-term benefits and risks of sodium-glucose cotransporter-2 inhibitors in type 2 diabetes: A systematic review and meta-analysis. JGIM, 2021; 37(2): 439-44, plus Supplementary materials at https://doi.org/10.1007/s11606-021-07227-0.

Selection criteria for the RCTs was that the study period was at least 52 weeks in duration. I assume the average duration of the studies was at least 2 years. So, an absolute risk reduction of mortality of 0.5% would be per 2+ years.

Author/s:

Mold, J. W.

Screening for Prediabetes and Type 2 Diabetes

Bethie Seay — Thu, 26 Aug 2021 05:00:00 +0000

Date Added:

August 26, 2021

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1001/jama.2021.12531

The U.S. Preventive Services Advisory Committee recommends screening nonpregnant adults aged 35 – 70 with BMI >25 for prediabetes and diabetes. While there is no recommendation regarding how often to screen, they mention that every 3 years seems reasonable based upon the evidence they reviewed.

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IMPORTANCE An estimated 13% of all US adults (18 years or older) have diabetes, and 34.5%
meet criteria for prediabetes. The prevalences of prediabetes and diabetes are higher in older
adults. Estimates of the risk of progression from prediabetes to diabetes vary widely, perhaps
because of differences in the definition of prediabetes or the heterogeneity of prediabetes.
Diabetes is the leading cause of kidney failure and new cases of blindness among adults in the
US. It is also associated with increased risks of cardiovascular disease, nonalcoholic fatty liver
disease, and nonalcoholic steatohepatitis and was estimated to be the seventh leading cause
of death in the US in 2017. Screening asymptomatic adults for prediabetes and type 2
diabetes may allow earlier detection, diagnosis, and treatment, with the ultimate goal of
improving health outcomes.
OBJECTIVE To update its 2015 recommendation, the USPSTF commissioned a systematic
review to evaluate screening for prediabetes and type 2 diabetes in asymptomatic,
nonpregnant adults and preventive interventions for those with prediabetes.
POPULATION Nonpregnant adults aged 35 to 70 years seen in primary care settings who have
overweight or obesity (defined as a body mass index 25 and 30, respectively) and no
symptoms of diabetes.
EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that screening for
prediabetes and type 2 diabetes and offering or referring patients with prediabetes to
effective preventive interventions has a moderate net benefit.
CONCLUSIONS AND RECOMMENDATION The USPSTF recommends screening for prediabetes
and type 2 diabetes in adults aged 35 to 70 years who have overweight or obesity. Clinicians
should offer or refer patients with prediabetes to effective preventive interventions.
(B recommendation)

Author/s:

US Preventative Services task Force