Perez, Jennifer

OBJECTIVE Glucagon-like peptide-1 (GLP-1) agonists are established therapeutics for weight loss that are increasingly used for BMI optimization prior to spine surgery. However, emerging evidence has suggested that GLP-1 agonists might reduce bone mineral density (BMD), increasing the risk of postoperative biomechanical complications. CT-based Hounsfield units (HUs) have gained popularity as a method for measuring spinal BMD. The aim of this study was to evaluate the effects of GLP-1 agonist–induced weight loss on spinal BMD as measured by opportunistic CT-based HUs. METHODS Patients who were treated with any GLP-1 agonist (2017–2022) for > 3 months were retrospectively identified. Patient body weight (BW), BMI, and HU measurements in the L1 vertebral body were measured before and after GLP-1 therapy. Patients were grouped according to the percentage of weight loss during GLP-1 therapy. One-way ANOVA was used to compare the mean changes in spinal HUs across the groups. RESULTS Among the 102 included patients, the mean ± standard error of the mean BW reduction was 14.5 ± 2.5 kg over 15.9 ± 1.2 months of GLP-1 agonist therapy. Of these, 7 patients (6.9%) lost > 20% BW (mean decrease of 31.9 ± 7.0 HU, p = 0.011), 14 (13.7%) lost 15%–20% BW (mean decrease of 19.1 ± 8.3 HU, p = 0.038), 14 (13.7%) lost 10%–15% BW (mean decrease of 12.2 ± 5.1 HU, p = 0.036), 24 (23.5%) lost 5%–10% BW (mean decrease of 15.7 ± 3.3 HU, p < 0.0001), 26 (25.5%) lost < 5% BW (mean decrease of 14.7 ± 6.0 HU, p = 0.022), and 17 (16.7%) gained BW during GLP-1 therapy (mean decrease of 6.3 ± 5.0 HU, p = 0.229). One-way ANOVA testing did not show a significant difference in HU reduction across the weight loss groups (F = 1.12, p = 0.355). In addition, there was a significant correlation between the decrease in L1 HUs and the duration of GLP-1 therapy (r = −0.38, p = 0.0001) but not the amount of weight loss (r = −0.18, p = 0.070). In the multivariate analysis, the duration of GLP-1 therapy (p = 0.032) was a significant independent predictor of vertebral HU reduction, but the amount of weight loss (p = 0.664) was not. CONCLUSIONS Despite similar pretreatment BW and HU measurements, all weight loss groups had significant decreases in vertebral HUs following GLP-1 agonist therapy, with a significant correlation observed between HU reduction and treatment duration. This suggests that long-term GLP-1 agonist therapy can significantly diminish spinal BMD regardless of the amount of weight loss achieved.

OBJECTIVE The Centers for Medicare & Medicaid Services (CMS) requires a low C-peptide level for insulin pump coverage unless the individual is β-cell autoantibody positive, which precludes coverage of automated insulin delivery (AID) systems for many people with type 2 diabetes. RESEARCH DESIGN AND METHODS In the Randomized Trial Evaluating the Efficacy and Safety of Control-IQ+ Technology in Adults With Type 2 Diabetes Using Basal-Bolus Insulin Therapy study evaluating the t:slim X2 insulin pump with Control-IQ+ technology, adults with insulin-treated type 2 diabetes were categorized into high C-peptide (n = 195) and low C-peptide (n = 59) groups based on CMS criteria. RESULTS In the AID group, mean HbA1c decreased from baseline by 0.8%, which was significantly greater than in the control group with both high (P &lt; 0.001) and low (P = 0.02) C-peptide levels. Results were similar in participants ≥65 years old. CONCLUSIONS The benefit of AID is present with high and low C-peptide levels. Thus, requiring a low C-peptide level as a prerequisite for AID therapy is not warranted.

OBJECTIVE To evaluate a regimen of inhaled Technosphere insulin (TI) plus insulin degludec in adults with type 1 diabetes, who prestudy were predominately using either an automated insulin delivery (AID) system or multiple daily insulin injections (MDI) with continuous glucose monitoring. RESEARCH DESIGN AND METHODS At 19 sites, adults with type 1 diabetes were randomly assigned to TI plus insulin degludec (N = 62) or usual care (UC) with continuation of prestudy insulin delivery method (N = 61) for 17 weeks. RESULTS Prestudy, AID was used by 48% and MDI by 45%. Mean ± SD HbA1c was 7.57% ± 0.97% at baseline and 7.62% ± 1.06% at 17 weeks in the TI group and 7.59% ± 0.80% and 7.54% ± 0.77%, respectively, in the UC group (adjusted difference 0.11%, 95% CI −0.10 to 0.33, P value for noninferiority = 0.01). HbA1c improved from baseline to 17 weeks by &gt;0.5% (5.5 mmol/mol) in 12 (21%) in the TI group and in 3 (5%) in the UC group and worsened by &gt;0.5% (5.5 mmol/mol) in 15 (26%) in the TI group and in 2 (3%) in the UC group. The most common TI side effect was a brief cough; eight participants discontinued TI due to side effects. CONCLUSIONS In adults with type 1 diabetes, HbA1c after 17 weeks with a regimen of TI and degludec was noninferior to UC, which consisted predominately of either AID or MDI. TI should be considered an option for people with type 1 diabetes, particularly those who are motivated to further reduce postprandial hyperglycemia.

OBJECTIVE To compare postprandial glucose excursions following a bolus with inhaled technosphere insulin (TI) or subcutaneous rapid-acting analog (RAA) insulin. RESEARCH DESIGN AND METHODS A meal challenge was completed by 122 adults with type 1 diabetes who were using multiple daily injections (MDI), a nonautomated pump, or automated insulin delivery (AID) and who were randomized to bolus with their usual RAA insulin (n = 61) or TI (n = 61). RESULTS The primary outcome, the treatment group difference in area under the curve for glucose &gt;180 mg/dL over 2 h, was less with TI versus RAA (adjusted difference −12 mg/dL, 95% CI −22 to −2, P = 0.02). With TI, the glucose excursion was smaller (P = 0.01), peak glucose lower (P = 0.01), and time to peak glucose shorter (P = 0.006). Blood glucose &lt;70 mg/dL occurred in one participant in each group. CONCLUSIONS Postmeal glucose excursion was smaller with TI than with RAA insulin in a cohort that included both AID and MDI users.