Patient and physician perspectives and experiences of basal insulin titration in type 2 diabetes in the United States: Cross-sectional surveys

Aim

Patient- and physician-associated barriers impact the effectiveness of basal insulin (BI) titration in the management of type 2 diabetes (T2D). We evaluated the experiences of patients with T2D and physicians with BI titration education.

Materials and Methods

In this observational, cross-sectional study, patients with T2D and physicians treating patients with T2D were identified by claims in the Optum Research Database and were invited to complete a survey. Eligible patients had 12 months of continuous health-plan enrolment with medical and pharmacy benefits during the baseline period, and recent initiation of BI therapy. Eligible physicians had initiated BI for ≥1 eligible patient with T2D during the past 6 months.

Results

In total, 416 patients and 386 physicians completed the survey. Ninety per cent of physicians reported treating ≥50 patients with T2D; 66% treated ≥25% of patients with BI. Whereas 74% of patients reported that BI titration was explained to them by a physician, 96% of physicians reported doing so. Furthermore, 20% of patients stated they were offered educational materials whereas 56% of physicians reported having provided materials. Physicians had higher expectations of glycaemic target achievement than were seen in the patient survey; their main concern was the patients' ability to titrate accurately (79%).

Conclusions

There is a marked difference in patients' and physicians' experiences of BI titration education. Novel tools and strategies are required to enable effective BI titration, with more educational resources at the outset, and ongoing access to tools that provide clear, simple direction for self-titration with less reliance on physicians/health care providers.     

Effects of initiation and titration of a single pre-prandial dose of insulin glulisine while continuing titrated insulin glargine in type 2 diabetes: a 6-month 'proof-of-concept' study

Aim: Stepwise intensification of insulin treatment to match the progressive decline of endogenous insulin secretion has been shown to be an effective management strategy in type 2 diabetes mellitus (T2DM). The efficacy of initiating and titrating a single bolus dose of insulin glulisine to baseline insulin glargine plus oral hypoglycaemic agents (OHAs) was investigated. Methods: This was a 6‐month, parallel‐group, randomized, open‐label, Phase IV study conducted in the US, UK and Russia. People with T2DM (HbA_1c 7.5–9.5%) using any basal insulin underwent a 3‐month run‐in period on insulin glargine titrated to optimize fasting blood glucose (BG) control. Those with HbA_1c >7.0% were randomized to either continue prior therapy (n = 57) or to add a single dose of insulin glulisine (n = 49) immediately prior to the main meal for a further 3 months. Two different titration algorithms were employed for the bolus dose, targeting 2‐h postprandial BG ≤135 mg/dL (≤7.5 mmol/l; Russia and UK) or pre‐meal/bedtime BG 100–120 mg/dl (5.5–6.7 mmol/l; US). Results: HbA_1c and fasting plasma glucose levels decreased during the run‐in period. In the 3 months after randomization, more participants in the basal‐plus‐bolus group reached HbA_1c <7.0% than the basal‐only control group (22.4 vs. 8.8%; p < 0.05), with significantly greater reduction of HbA_1c (?0.37 vs. ?0.11%; p = 0.0290). Rates of hypoglycaemia and mean weight change were comparable between the treatment groups. Conclusions: In people with T2DM inadequately controlled on basal insulin plus OHAs, adding a single injection of insulin glulisine prior to the main meal significantly improves glucose control without undesired side effects.     

Relationship between treatment persistence and A1C trends among patients with type 2 diabetes newly initiating basal insulin

This study examines the relationship between glycated haemoglobin (A1C) levels and treatment persistence with, or time to discontinuation of, basal insulin in patients with type 2 diabetes (T2D) newly initiating insulin. Claims data were extracted from the Optum Clinformatics database from January 2010 to June 2015. Adult patients with T2D initiating insulin glargine 100 U/mL (Gla‐100) or insulin detemir (DET) with ≥1 A1C measurement during 12‐month baseline and 18‐month follow‐up periods were included. Patients with a refill gap of >90 days were considered non‐persistent; otherwise, patients were considered persistent with insulin. The main outcome was A1C, measured closest to the end of each quarter during the follow‐up period. A total of 3993 of 109 934 patients met the inclusion criteria (43.0% persistent; 57.0% non‐persistent). Persistent patients were older (54.7 vs 52.7 years; P < .001), were more likely to be male (59.4% vs 54.4%; P = .002), and had significantly lower mean unadjusted A1C values at 18 months (8.26% vs 8.60%; P < .001) and quarterly. Only 43.0% of adults initiating basal insulin persisted with treatment for 18 months, with earlier discontinuation associated with higher A1C.     

Titratable fixed-ratio combination of basal insulin plus a glucagon-like peptide-1 receptor agonist: A novel,simplified alternative to premix insulin for type 2 diabetes

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon-like peptide-1 receptor agonist (GLP-1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real-world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed-ratio combinations (FRCs) of basal insulin and GLP-1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta-analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head-to-head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP-1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP-1 RAs as an alternative treatment option.     

Fixed-ratio combination of insulin degludec and liraglutide (IDegLira) improves cardiovascular risk markers in patients with type 2 diabetes uncontrolled on basal insulin

In this post hoc analysis we investigated the effects of insulin degludec/liraglutide fixed-ratio combination (IDegLira) versus comparators on cardiovascular (CV) risk markers in participants in the DUAL II (vs. insulin degludec), DUAL V (vs. insulin glargine 100 units/mL) and DUAL VII (vs. basal–bolus therapy) trials, grouped by sex, age (<65 years, ≥65 years) and diabetes duration (<10 years, ≥10 years). Treatment contrasts were in favour of IDegLira in many subgroups for changes from baseline in glycated haemoblogin (DUAL II, DUAL V), body weight (all three trials), systolic blood pressure (BP; all three trials), HDL cholesterol (DUAL VII) and LDL cholesterol (DUAL II, DUAL V). Higher heart rates were seen with IDegLira versus comparators (all three trials) plus significantly higher diastolic BP in men (DUAL V). Differences in treatment effect were seen between sexes in waist circumference (DUAL II), systolic BP (DUAL II, DUAL V) and triglycerides (DUAL VII), and between diabetes durations in LDL cholesterol (DUAL V). In conclusion, IDegLira is associated with a general improvement in CV risk markers compared with basal insulin or basal–bolus therapy after 26 weeks of treatment.     

Efficacy of two telemonitoring systems to improve glycaemic control during basal insulin initiation in patients with type 2 diabetes: The TeleDiab-2 randomized controlled trial

TeleDiab-2 was a 13-month randomized controlled trial evaluating the efficacy and safety of two telemonitoring systems to optimize basal insulin (BI) initiation in subjects with inadequately controlled type 2 diabetes (HbA1c, 7.5%-10%). A total of 191 participants (mean age 58.7 years, mean HbA1c 8.9%) were randomized into three groups: group 1(G1, standard care, n = 63), group 2 (G2, interactive voice response system, n = 64) and group 3 (G3, Diabeo-BI app software, n = 64). The two telemonitoring systems proposed daily adjustments of BI doses, in order to facilitate the achievement of fasting blood glucose (FBG) values targeted at ~100 mg/dL. At 4 months follow-up, HbA1c reduction was significantly higher in the telemonitoring groups (G2: −1.44% and G3: −1.48% vs. G1: −0.92%; P < 0.002). Moreover, target FBG was reached by twice as many patients in the telemonitoring groups as in the control group, and insulin doses were also titrated to higher levels. No severe hypoglycaemia was observed in the telemonitoring groups and mild hypoglycaemia frequency was similar in all groups. In conclusion, both telemonitoring systems improved glycaemic control to a similar extent, without increasing hypoglycaemic episodes.     

The importance of the initial period of basal insulin titration in people with diabetes

Achieving target glycaemic control is essential in people with diabetes to minimize the risk of long-term complications, and many people with type 2 diabetes will ultimately require basal insulin (BI) therapy to achieve their individualized glycaemic targets. Usually, the first 12 weeks following initiation of BI therapy represents the period when the greatest dose increases and glycaemic reductions occur. Effective glycaemic control combined with minimizing the risk of hypoglycaemia is important to enable the achievement of glycaemic control in the longer term. However, substantial therapeutic inertia exists in clinical practice, both in initiation and up-titration of BI, owing to patient-, physician- and healthcare system-related barriers, including fear of hypoglycaemia and the perception of a burdensome regimen. The more prolonged duration of action, reduced glycaemic variability and lower risk of hypoglycaemia seen with second-generation versus first-generation BI analogues may help alleviate patients’ and physicians’ concerns and facilitate titration. In turn, optimal BI titration and subsequent metabolic benefits may help improve therapy adherence and self-management. This review details the clinical implications of prompt titration of BI to achieve early glycaemic control, and the importance of minimizing hypoglycaemia risk within the initial titration period. Facilitation of patients’ self-management of BI is also addressed.     

Type 2 diabetes in young adults in Central Auckland: demography and complications

Background

Type 2 diabetes (T2D) in young adults is associated with a high risk of diabetes complications.

Aims

To investigated the demography and the emergence of complications of young adults with T2D in the central Auckland region where there has been substantial immigration.

Methods

In total, 310 young adults with T2D (<40 years) were registered with the Auckland Diabetes Centre in 2015. We documented demographic, anthropometric and metabolic variables and prevalence and the emergence of complications.

Results

Three demographic groups accounted for 243 participants (78%): 135 (44%) were migrants of Asian or Pacific Island origin, diagnosed a median 9 years after migration at a mean age of 28 ± 6 years; 88 (29%) were New Zealand‐born Pāsifika descent, with a high prevalence of morbid obesity and 37 (12%) had major mental illness or intellectual disability. At diagnosis, the median HbA1c was 80 mmol/mol, and in 28%, it was ≥100 mmol/mol. A median 6 years after diagnosis, 56% had some degree of retinopathy, with the prevalence related both to the duration of diabetes and glycaemic control (P = 0.001). Forty‐four percent of subjects had abnormal albuminuria at diagnosis (12% with macroalbuminuria). Increased albuminuria was strongly associated with obesity (P = 0.002). The development of CKD stages 4–5 was related both to the severity of retinopathy and degree of albuminuria at diagnosis (P = 0.0001). Major cardiovascular events were related to the severity of retinopathy at diagnosis (P = 0.0001).

Conclusions

New migrants, New Zealand‐born Pāsifika and patients with mental illness or an intellectual disability comprise the bulk of young onset T2D. The disease is aggressive, and by the age of 40, patients are already developing advanced complications.     

Albumin-bound basal insulin analogues (insulin detemir and NN344): comparable time-action profiles but less variability than insulin glargine in type 2 diabetes

AIM: This study compared the time-action profiles of the novel albumin-bound basal insulin analogue NN344 with those of insulin detemir and insulin glargine in individuals with type 2 diabetes. METHODS: Twenty-seven insulin-treated men with type 2 diabetes [body mass index 30.8 +/- 2.6 kg/m(2) (mean +/- s.d.), haemoglobin A(1c) 7.6 +/- 1.1%] were enrolled in this randomized, double-blind trial and participated in six euglycaemic glucose clamp experiments [target blood glucose (BG) 5 mmol/l] each. Participants received NN344 in three experiments at a dose of 0.8, 1.6 and 2.8 dosing units (DU) (1 DU corresponds to 6 nmol NN344) per kilogram of body weight. In the other three experiments, the participants received 0.4, 0.8 and 1.4 U/kg of either insulin detemir or insulin glargine. The insulin preparations were characterized with regards to their effects on glucose infusion rates (GIRs) (in particular duration of action and within-subject and between-subject variabilities), BG, C-peptide, free fatty acids (FFA), endogenous glucose production (EGP) and peripheral glucose uptake (PGU) over 24 h post-dose. RESULTS: The mean GIR profiles for all three preparations were similar in shape/flatness and showed increasing effect (area under the curve for GIR: AUC-GIR(total)) with increasing dose [low dose: 647 +/- 580, 882 +/- 634, 571 +/- 647 mg/kg (insulin detemir vs. NN344 vs. insulin glargine]; medium dose: 1203 +/- 816, 1720 +/- 1109, 1393 +/- 1203 mg/kg and high dose: 2171 +/- 1344, 3119 +/- 1549, 2952 +/- 2028 mg/kg; p = 0.48]. The duration of action increased with rising doses of all insulin preparations, without major differences between treatments. BG remained below 7 mmol/l in nearly all the experiments. Within-subject variability was lower for the albumin-bound insulin analogues, insulin detemir and NN344, than for insulin glargine (p < 0.0001). Between-subject variability did not differ between treatments, nor did the effects on BG, C-peptide, FFA, EGP or PGU. CONCLUSIONS: In individuals with type 2 diabetes, the time-action profiles and the duration of action of the albumin-bound insulin analogues, insulin detemir and NN344, were comparable with those of insulin glargine, whereas within-subject variability in the metabolic effect was significantly lower. Therefore, insulin detemir and NN344 seem to be as well suited as insulin glargine for once-daily administration in type 2 diabetes. The better predictability may be an important characteristic of the albumin-bound analogues as insulin detemir has already been shown to improve hypoglycaemia.     

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10–<15, ≥15–<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.