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Management of Outpatients With Diabetes at High Risk of Hypoglycemia

Author/s: 
Celeste C Thomas, Karishma Chopra, Andrew M Davis

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

Keywords 
diabetes Diabetes and Endocrinology Endocrinology insulin

What Should I Know About Injectable Weight-Loss Medications?

Author/s: 
Andrew Kraftson, Dina Griauzde

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.

Keywords 
Semaglutide tirzepatide obesity weight loss Feeding and Eating Disorders

Heart Failure With Preserved Ejection Fraction

Author/s: 
Redfield, Margaret, Borlaug, Barry

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.

Keywords 
heart failure glucose Stroke Volume physical exertion hospitalization

Weight Loss Outcomes Associated With Semaglutide Treatment for Patients With Overweight or Obesity

Author/s: 
Ghusn, W., De la Rosa, A., Sacoto, D.

Importance No retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).

Objective To study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity.

Design, Setting, and Participants This cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded.

Exposures Weekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months.

Main Outcomes and Measures The primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months.

Results The study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005).

Conclusions and Relevance The results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.

Keywords 
Cohort Studies overweight Retrospective Studies middle aged weight loss

Axillary and inguinal erythrasma

Author/s: 
Riquelme, R. L., Moyano, E. G.

A 50-year-old man presented to the dermatology department with a 1-year history of itchy axillary and groin lesions. He had been treated with a topical antifungal preparation (cyclopyroxolamin), without improvement, by his family physician, who had suspected fungal intertrigo. On physical examination, we observed well-circumscribed, erythematous, brownish, scaly plaques affecting both armpits and the groin area bilaterally (Figure 1). To rule out superficial mycoses, we examined skin scrapings from the infected site under direct microscopy after potassium hydroxide preparation. We did not find any signs of fungal infection and did not isolate any dermatophytes in Sabouraud agar.

The relationship between exacerbated diabetic peripheral neuropathy and metformin treatment in type 2 diabetes mellitus

Author/s: 
Hashem, Manal Mohammed, Esmael, Ahmed, Nassar, Abdelfattah Kasem, El-Sherif, Mohammed

Metformin-treated diabetics (MTD) showed a decrease in cobalamin, a rise in homocysteine, and methylmalonic acid, leading to accentuated diabetic peripheral neuropathy (DPN). This study aimed to determine whether or not metformin is a risk factor for DPN. We compared MTD to non-metformin-treated diabetics (NMTD) clinically using the Toronto Clinical Scoring System (TCSS), laboratory (methylmalonic acid, cobalamin, and homocysteine), and electrophysiological studies. Median homocysteine and methylmalonic acid levels in MTD vs. NMTD were 15.3 vs. 9.6 µmol/l; P < 0.001 and 0.25 vs. 0.13 µmol/l; P = 0.02, respectively with high statistical significance in MTD. There was a significantly lower plasma level of cobalamin in MTD than NMTD. Spearman's correlation showed a significant negative correlation between cobalamin and increased dose of metformin and a significant positive correlation between TCSS and increased dose of metformin. Logistic regression analysis showed that MTD had significantly longer metformin use duration, higher metformin dose > 2 g, higher TCSS, lower plasma cobalamin, and significant higher homocysteine. Diabetics treated with metformin for prolonged duration and higher doses were associated with lower cobalamin and more severe DPN.

Keywords 
diabetes, type 2 metformin insulin Metformin Treatment

CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM - 2020 EXECUTIVE SUMMARY

Author/s: 
Garber, A.J., Handelsman, Y., Grunberger, G., Einhorn, D., Abrahamson, M.J., Barzilay, J.I., Blonde, L., Bush, M.A.

No abstract available.

Diabetes Management in Chronic Kidney Disease: Synopsis of the 2020 KDIGO Clinical Practice Guideline

Author/s: 
Navaneethan, Sankar D., Zougas, Sophia, Caramori, M.L., Chan, Juliana C.N., Heerspink, Hiddo J.L., Hurst, Clint, Liew, Adrian, Michos, Erin D., Olowu, Wasiu A., Sadusky, Tami, Tandon, Nikhil, Tuttle, Katherine R., Wanner, Christoph, Wilkens, Katy G., Lytvyn, Lyubov, Craig, Jonathan C., Tunnicliffe, David J., Howell, Martin, Tonelli, Marcello, Cheung, Michael, Earley, Amy, Rossing, Peter, De Boer, Ian H., Khunti, Kamlesh

Description: The Kidney Disease: Improving Global Outcomes (KDIGO) organization developed a clinical practice guideline in 2020 for the management of patients with diabetes and chronic kidney disease (CKD).

Methods: The KDIGO Work Group (WG) was tasked with developing the guideline for diabetes management in CKD. It defined the scope of the guideline, gathered evidence, determined systematic review topics, and graded evidence that had been summarized by an evidence review team. The English-language literature searches, which were initially done through October 2018, were updated in February 2020. The WG used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to appraise evidence and rate the strength of the recommendations. Expert judgment was used to develop consensus practice points supplementary to the evidence-based graded recommendations. The guideline document underwent open public review. Comments from various stakeholders, subject matter experts, and industry and national organizations were considered before the document was finalized.

Recommendations: The guideline includes 12 recommendations and 48 practice points for clinicians caring for patients with diabetes and CKD. This synopsis focuses on the key recommendations pertinent to the following issues: comprehensive care needs, glycemic monitoring and targets, lifestyle interventions, antihyperglycemic therapies, and educational and integrated care approaches.

Keywords 
Medical dialysis clucose proteins renal diseases Hypoglycemics Treatment guidelines chronic kidney disease type 2 diabetes Kidneys

Dapagliflozin in Patients with Chronic Kidney Disease

Author/s: 
DAPA-CKD Trial Committees and Investigators

Abstract

Background: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known.

Methods: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes.

Results: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed.

Conclusions: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).

Copyright © 2020 Massachusetts Medical Society.

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