Beneficial Effect of Remote Glucose Monitoring and Computerized Insulin Dose Adjustment Algorithms Independent of Insulin Dose Increases in Sizeable Minorities of Patients.

This article describes a program through which interactions every 2-3 weeks between patients and primary care clinicians (PCCs), with recommendations based on analysis of remote glucose monitoring by computerized insulin dose adjustment algorithms, significantly improved diabetes control. Insulin doses increased by 30% in the majority of patients. A sizeable minority (36%) had a decrease or no increase in insulin doses, but still showed an improvement in diabetes control. Frequent interactions allowed PCCs the opportunity to recognize and address medication nonadherence.

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk.

SOURCE CITATION: Garvey WT, Frias JP, Jastreboff AM, et al; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023;402:613-626. 37385275.

Should Prediabetes be Treated Pharmacologically?

OBJECTIVE: In this commentary I will evaluate whether prediabetes should be treated pharmacologically. To consider this question, certain information concerning prediabetes is relevant. BACKGROUND INFORMATION: (1) Prediabetes is not independently associated with cardiovascular disease; the other factors in the metabolic syndrome increase that risk; (2) various tests and criteria for diagnosing prediabetes are recommended, yielding prevalences varying from 6% to 38% depending on which are used; (3) one-third of patients with prediabetes revert to normal over time; (4) up to two-thirds of patients with prediabetes do not develop diabetes; (5) people with prediabetes have insulin resistance and impaired insulin secretion; (6) although pharmacological treatment of the dysglycemia temporarily lowers it, when the drugs are discontinued, incident diabetes develops similarly as that in those who received placebos; (7) when the drugs are discontinued, there are no changes in insulin resistance or impaired insulin secretion; (8) incident diabetes was similar at 10 years in people remaining on metformin in the Diabetes Prevention Program Outcome Study compared with those who did not receive the drug; (9) no current drugs will directly increase insulin secretion (except sulfonylureas and glinides which have not been used to treat prediabetes because of hypoglycemia concerns); (10) sufficient weight loss to lower insulin resistance by nutritional means is challenging and especially difficult to maintain. CONCLUSIONS: Pharmacological treatment of the dysglycemia of prediabetes is not warranted. On the other hand, the ability of high doses of glucagon-like peptide (GLP)-1 receptor agonists and the combination of a GLP-1 receptor agonist and the glucose-dependent insulinotropic polypeptide (GIP) to lower weight by 15% and 20%, respectively, deserves consideration for the treatment of prediabetes. This amount of weight loss should decrease insulin resistance, allowing endogenous insulin secretion to be more effective and lower the risk for developing diabetes.

The Role of Prediabetes in the Metabolic Syndrome: Guilt by Association.

The metabolic syndrome (MetS) is a cluster of risk factors for cardiovascular disease (CVD). Prediabetes is defined by either impaired glucose tolerance or by one of the more sensitive or more stringent criterion for impaired fasting glucose (IFG) or HbA1c levels that have been promulgated over the years. IFG is one of the risk factors for CVD included in the definition of the MetS. However, there is very little evidence that IFG is independently associated with CVD regardless of which criterion is used for its diagnosis. The CVD risk of the MetS is related to the other risk factors of central obesity, hypertension, elevated triglyceride, and low high-density lipoprotein cholesterol levels. If the components of the MetS are supposed to be risk factors for CVD, the dysglycemia of prediabetes should not be included in its definition.

In adults with obesity without diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk.

SOURCE CITATION: Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022;387:205-16. 35658024.

A Conversation on an Effective, Straightforward, Quantitative Approach to the Outpatient Use of Insulin.

For primary care providers, using insulin can present challenges that can be met by a straightforward approach using the following principles. Depending on when it is injected, each component of the insulin regimen has a maximal effect on a specific period of the 24-hour cycle (e.g., overnight, morning, afternoon, or evening). The glucose pattern in that period determines whether the dose of that component of the insulin regimen requires adjusting. Regarding which insulin types and insulin regimens to use, human insulin (NPH and regular) is as effective as analog insulins, and a two-injection intensified insulin regimen is as effective as a four-injection regimen.

Historical review of the diagnosis of prediabetes/intermediate hyperglycemia: Case for the international criteria.

In 1997, the ADA recommended an IFG criterion for diagnosing prediabetes/intermediate hyperglycemia of FPG concentrations of 6.1-6.9 mmol/L (110-125 mg/dL). In 2003, they lowered it to 5.6-6.9 mmol/L (100-125 mg/dL) to equalize developing diabetes between IGT and IFG. International organizations accepted the first IFG criterion but not the second. The ADA subsequently recommended HbA1c levels for diagnosing prediabetes/intermediate hyperglycemia of 39-47 mmol/mol (5.7-6.4%) based on a model that utilized the composite risk of developing diabetes and CVD. However, the evidence that the intermediate hyperglycemia that defines prediabetes is independently associated with CVD is weak. Rather, the other risk factors for CVD in the metabolic syndrome are responsible. The WHO opined that prediabetes/intermediate hyperglycemia could not be diagnosed by HbA1c levels but the Canadians and Europeans recommended its diagnosis by values of 42-47 mmol/mol (6.0-6.4%). With the ADA criteria, approximately one-half of people are normal on re-testing, one-third spontaneously revert to normal over time and two-thirds never develop diabetes in their lifetimes. The international criteria for prediabetes/intermediate hyperglycemia increase the risk of developing diabetes and might motivate these individuals to more seriously undertake lifestyle interventions as a preventive measure.

Effect of Diabetes-Trained Nurse Practitioners on Glycemic Outcomes: Their Suggested Use in Busy Primary Care Practices.

A Federally Qualified Health Center received ongoing external support for half-time salaries for two nurse practitioners to treat people with poorly controlled diabetes (A1C >9.0%) in the clinic's diabetes program using approved detailed treatment protocols. Patients were treated for 1 year and graduated from this program if their A1C fell to <7.5%. Ninety-one percent graduated, and treatment was deemed to have failed in 9% who did not achieve an A1C <7.5% by the end of the year of treatment. The suggestion is made to assign a specially trained diabetes nurse or physician assistant to serve many primary care providers at important clinical junctures to improve diabetes outcomes throughout busy primary care practices.

Effective use of computerized insulin dose adjustment algorithms on continuous glucose monitoring results by a clinical pharmacist - Proof-of-concept.

Highlights A clinical pharmacist using recommendations of Food and Drug Administration-cleared computerized insulin dose adjustment algorithms based on analyses of glucose readings from continuous glucose monitoring (Abbot Free Style Pro) in 13 poorly controlled insulin-requiring diabetic patients increased time in target range of 3.9 to 10.0 mmol/L from 29% to 51% and decreased time in range of >13.9 mmol/L from 43% to 23% (both P = 0.01) after 3 months. Glycated hemoglobin (HbA1c) levels (±SD) fell from 102 (±15) to 67 (±10) mmol/mol (P < 10-6 ).

Metformin Should Not Be Used to Treat Prediabetes.

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110-125 vs. 100-109 mg/dL (6.1-6.9 vs. 5.6-6.0 mmol/L) and A1C levels 6.0-6.4% (42-46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.