Adjunct Therapy in Type 1 Diabetes: A Survey to Uncover Unmet Needs and Patient Preferences Beyond HbA1c Measures.

Background: Adjunct therapy can help patients with type 1 diabetes achieve glycemic goals while potentially mitigating some of the side effects of insulin. In this study, we used a patient survey to identify the unmet needs in type 1 diabetes therapy, patient views of treatment benefit-risk trade-offs, and patient preferences for the use of an adjunct therapy. Methods: A quantitative survey was sent to 2084 adults with type 1 diabetes in November 2017. "Jobs-to-be-done" and conjoint analyses were performed on survey responses to identify unmet needs and the importance of treatment-associated benefits and risks to patients. A 5-point Likert scale measured the importance and satisfaction with patients' current therapy, and with gaps relating to unmet needs. In the conjoint analysis, patients were asked to choose between "packages" of attributes of two doses of adjunct therapy (200 and 400 mg) and placebo, based on established benefits and side effects. Results: A total of 1313 patients (63%) responded. The greatest unmet needs identified were simplifying treatment, lowering/maintaining glycated hemoglobin (HbA1c), reducing mental effort, and increasing time in range (TIR). Conjoint analysis showed that reductions in body weight and TIR had the highest attribute importance (25% and 18%, respectively). The majority (93%) of patients had a preference for the adjunct therapy (either dose) over placebo. Conclusions: This survey highlights the importance of measures beyond HbA1c, such as treatment simplification and TIR, and patient preference for adjunct therapies that help address unmet needs in type 1 diabetes treatment.

Early treatment revisions by addition or switch for type 2 diabetes: impact on glycemic control, diabetic complications, and healthcare costs.

BACKGROUND: The study examined the prevalence of early treatment revisions after glycosylated hemoglobin (HbA1c) ≥9.0% (75 mmol/mol) and estimated the impact of early treatment revisions on glycemic control, diabetic complications, and costs. RESEARCH DESIGN AND METHODS: A retrospective cohort study of administrative claims data of plan members with type 2 diabetes and HbA1c ≥9.0% (75 mmol/mol) was completed. Treatment revision was identified as treatment addition or switch. Glycemic control was measured as HbA1c during 6-12 months following the first qualifying HbA1c ≥9.0% (75 mmol/mol) laboratory result. Complications severity (via Diabetes Complication Severity Index (DCSI)) and costs were measured after 12, 24, and 36 months. Unadjusted comparisons and multivariable models were used to examine the relationship between early treatment revision (within 90 days of HbA1c) and outcomes after controlling for potentially confounding factors measured during a 12-month baseline period. RESULTS: 8463 participants were included with a mean baseline HbA1c of 10.2% (75 mmol/mol). Early treatment revision was associated with greater reduction in HbA1c at 6-12 months (-2.10% vs -1.87%; p<0.001). No significant relationship was observed between early treatment revision and DCSI at 12, 24, or 36 months (p=0.931, p=0.332, and p=0.418). Total costs, medical costs, and pharmacy costs at 12, 24, or 36 months were greater for the early treatment revision group compared with the delayed treatment revision group (all p<0.05). CONCLUSIONS: The findings suggest that in patients with type 2 diabetes mellitus, treatment revision within 90 days of finding an HbA1c ≥9.0% is associated with a greater level of near-term glycemic control and higher cost. The impact on end points such as diabetic complications may not be realized over relatively short time frames.

Comparison of insulin aspart and lispro: pharmacokinetic and metabolic effects.

OBJECTIVE: To compare insulin levels and actions in patients with type 1 diabetes after subcutaneous injection of the rapid-acting insulin analogs aspart and lispro. RESEARCH DESIGN AND METHODS: Seven C-peptide-negative patients with type 1 diabetes (two men and five women) were studied at the General Clinical Research Center at Temple University Hospital two times, 1 month apart. Their plasma glucose was normalized overnight by intravenous infusion of insulin. The next morning, they received subcutaneous injections of either aspart or lispro (9.4 +/- 1.9 U) in random order. For the next 4-5 h, their plasma glucose was clamped at approximately 5.5 mmol/l with a variable infusion of 20% glucose. The study was terminated after 8 h. RESULTS: Both insulin analogs produced similar serum insulin levels (250-300 pmol/l) at approximately 30 min and disappeared from serum after approximately 4 h. Insulin aspart and lispro had similar effects on glucose and fat metabolism. Effects on carbohydrate metabolism (glucose uptake, glucose oxidation, and endogenous glucose production) peaked after approximately 2-3 h and disappeared after approximately 5-6 h. Effects on lipid metabolism (plasma free fatty acid, ketone body levels, and free fatty acid oxidation) appeared to peak earlier (at approximately 2 h) and disappeared earlier (after approximately 4 h) than the effects on carbohydrate metabolism. CONCLUSIONS: We conclude that both insulin aspart and lispro are indistinguishable from each other with respect to blood levels and that they are equally effective in correcting abnormalities in carbohydrate and fat metabolism in patients with type 1 diabetes.

Efficacy and tolerability of self-titrated biphasic insulin aspart 70/30 in patients aged >65 years with type 2 diabetes: an exploratory post hoc subanalysis of the INITIATEplus trial.

BACKGROUND: The Initiation of Insulin to reach A1C Target (INITIATEplus) trial studied the effect of self-titrating biphasic insulin aspart 70/30 (BiAsp 30) twice daily during 24 weeks in insulin-naïve patients with type 2 diabetes who were poorly controlled by oral medication, and originally randomized according to frequency of dietary counseling interventions. OBJECTIVE: The purpose of this study was to compare the efficacy and tolerability of biphasic insulin aspart 70/30 (BIAsp 30, NovoLog Mix 70/30) in INITIATEplus patients ≤65 versus >65 years old, irrespective of dietary counseling frequency, and to test the hypothesis that self-titrating BIAsp 30 in patients >65 years old could be well-tolerated and effective in this age group. METHODS: An exploratory post hoc subanalysis, using standard statistical methods, was performed on patients stratified according to age. Data collected from 3492 patients in the intent-to-treat population who were ≤65 years old and 716 patients who were >65 years old compared glycosylated hemoglobin (HbA(1c)) and plasma glucose changes from baseline. Hypoglycemia rates and adverse event (AE) incidence were compared for the tolerability population of 4007 patients ≤65 years old and 805 patients >65 years old. RESULTS: Baseline-adjusted HbA(1c) changes for patients ≤65 versus >65 years old were -2.38% versus -2.73% (P < 0.0001), with final HbA(1c) achieving 7.55% and 7.06%, respectively. Thirty-nine percent of patients ≤65 years old achieved HbA(1c) ≤7% compared with 51% of patients >65 years old. Baseline-adjusted fasting plasma glucose decreases were greater for the >65 year old population (85.2 vs 91.2 mg/dL; P = 0.004; ≤65 vs >65 years old, respectively). Minor hypoglycemia was reported in 9.7% and 7.7% of patients ≤65 versus >65 years old, respectively (0.52 vs 0.41 episodes per patient per year [ppy]; P = 0.01). Major hypoglycemia occurred in 1.5% and 3.1% of patients (0.05 vs 0.14 episodes ppy, ≤65 vs >65 years old, respectively; P < 0.0001). Nocturnal major hypoglycemia was reported for 0.4% and 0.6% of patients (P = 0.0028), whereas nocturnal minor hypoglycemia was reported for 3.8% and 2.6% (P = 0.007) of patients ≤65 and >65 years old, respectively. AEs were reported for 24% and 28% of patients ≤65 and >65 years old, respectively, serious AEs were reported for 4% and 9% of patients, respectively, and AE-related withdrawals were reported for 1.3% and 2% of patients, respectively. CONCLUSIONS: Self-titrated biphasic insulin aspart 70/30 was found to be well-tolerated and effective in type 2 diabetes patients >65 years old, as well as in patients ≤65 years old. HbA(1c) and fasting plasma glucose decreases were significantly (P < 0.05) higher for patients >65 years old versus patients ≤65 years old. Tolerability was indicated by major and minor hypoglycemia rates at or below <0.5 episodes ppy in both age groups. Overall rates of AE and serious AEs were higher among patients > 65 years; withdrawals related to AEs were 2% compared with 1.3% in the younger age group.