[Show abstract][Hide abstract] ABSTRACT: Elderly patients with diabetes are more vulnerable to the occurrence and effects of hypoglycaemia; therefore, treatments with low risk of hypoglycaemia are preferred in this population. This study aimed to compare hypoglycaemia rates between insulin degludec (IDeg) and insulin glargine (IGlar) in elderly patients.
Hypoglycaemia data from patients ≥65 years of age with type 1 (T1DM) or type 2 (T2DM) diabetes from seven randomised, treat-to-target phase IIIa trials were used to compare IDeg and IGlar in a pre-planned meta-analysis. Overall, 917/4345 (21 %) randomised patients in the seven trials were elderly (634 IDeg, 283 IGlar). Overall confirmed hypoglycaemia was defined as <3.1 mmol/L or severe hypoglycaemia (symptoms requiring external assistance). Nocturnal hypoglycaemia included confirmed episodes from 0001 to 0559 hours (inclusive). Treatment comparisons of hypoglycaemia in T1DM patients were not performed due to low numbers of elderly patients with T1DM randomised (43 IDeg, 18 IGlar); statistical comparisons were also not made for severe hypoglycaemia due to the low number of events.
In elderly patients with T2DM, the rate of overall confirmed hypoglycaemia was significantly lower with IDeg than IGlar [estimated rate ratio (ERR) 0.76 (0.61; 0.95)95 % CI]; nocturnal confirmed hypoglycaemia was also significantly lower with IDeg [ERR 0.64 (0.43; 0.95)95 % CI]. Confirmed hypoglycaemia occurred in the majority of T1DM patients, whereas severe episodes occurred infrequently and at similar rates in both treatment groups in T1DM and T2DM.
Results of this pre-planned meta-analysis in elderly patients with diabetes demonstrate a significant reduction in hypoglycaemic events with IDeg relative to IGlar.
[Show abstract][Hide abstract] ABSTRACT: Insulin degludec (IDeg) is a new ultra-long-acting basal insulin shown to have low day-to-day variability in a euglycemic clamp study. In this post-hoc meta-analysis of patients with T2D, we compared day-to-day variability in mean selfmeasured blood glucose (derived from 9-point profiles; 9P-SMPG) between IDeg and insulin glargine (IGlar).
Canadian Journal of Diabetes 10/2013; 37S4(3):S26. DOI:10.1016/j.jcjd.2013.08.079 · 2.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Results of an exploratory phase 2 study showed that insulin degludec, a basal insulin with an action profile of longer than 42 h, provided similar glycaemic control when injected three times a week (IDeg 3TW) to once-daily insulin glargine (IGlar OD). To provide further evidence, we did two phase 3 trials to compare the efficacy and safety of IDeg 3TW with IGlar OD in insulin-naive patients with type 2 diabetes.
In two 26 week, randomised, open-label, parallel group, non-inferiority trials IDeg was injected Monday, Wednesday, and Friday before breakfast (IDeg 3TWAM) in the AM trial (94 sites in seven countries) or with the evening meal (IDeg 3TWPM) in the PM trial (89 sites in seven countries), and compared with IGlar OD. Adults with type 2 diabetes (HbA1c 7·0-10·0%; body-mass index ≤45 kg/m(2)) were randomly allocated (1:1) without stratification by a central interactive response system to IDeg 3TW or IGlar OD. Both groups continued taking metformin with or without dipeptidyl peptidase-4 inhibitors. Insulin was titrated to achieve a prebreakfast self-monitored blood glucose (SMBG) concentration of between 3·9 and less than 5·0 mmol/L. The primary outcome was non-inferiority of IDeg 3TW compared with IGlar OD, as assessed by change in HbA1c from baseline to 26 weeks (non-inferiority limit of 0·4%) by ANOVA in an intent-to-treat analysis (full analysis set). These trials are registered with ClinicalTrials.gov, numbers NCT01068678 and NCT01076647.
We recruited 460 patients for the AM trial (IDeg 3TWAM, n=230; IGlar OD, n=230) and 467 patients for the PM trial (IDeg 3TWPM, n=233; IGlar OD, n=234). After 26 weeks, mean HbA decreased by 0·9% (IDeg 3TWAM) and 1·3% (IGlar OD) in the AM trial, and by 1·1% (IDeg 3TWPM) and 1·4% (IGlar OD) in the PM trial. Non-inferiority was not confirmed in either trial (estimated treatment difference [IDeg 3TWAM-IGlar OD] 0·34%, 95% CI 0·18-0·51; [IDeg 3TWPM-IGlar OD] 0·26%, 0·11-0·41). Across the two trials, rates of confirmed hypoglycaemia (SMBG <3·1 mmol/L or severe [needing assistance]) ranged from 1·0 to 1·6 episodes per patient-year and were similar for IDeg 3TWAM and IGlar OD (estimated rate ratio [ERR] 1·04, 95% CI 0·69-1·55), but higher for IDeg 3TWPM than for IGlar OD (ERR 1·58, 1·03-2·43). The rate of nocturnal confirmed hypoglycaemia was higher for IDeg 3TWAM than for IGlar OD (ERR 2·12, 1·08-4·16); we noted no significant difference between IDeg 3TWPM and IGlar OD (ERR 0·60, 0·21-1·69).
The inferior glycaemic control and increased risk of hypoglycaemia with IDeg 3TW compared with IGlar OD do not support a three-times-weekly dosing regimen.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
The requirement to inject current basal insulin analogs at a fixed time each day may complicate adherence and compromise glycemic control. This trial evaluated the efficacy and safety of varying the daily injection time of insulin degludec (IDeg), an ultra-long-acting basal insulin.RESEARCH DESIGN AND METHODS
This 26-week, open-label, treat-to-target trial enrolled adults (≥18 years) with type 2 diabetes who were either insulin-naïve and receiving oral antidiabetic drugs (OADs) (HbA(1c) = 7-11%) or previously on basal insulin ± OAD(s) (HbA(1c) = 7-10%). Participants were randomized to 1) once-daily IDeg in a prespecified dosing schedule, creating 8-40-h intervals between injections (IDeg OD Flex; n = 229); 2) once-daily IDeg at the main evening meal (IDeg OD; n = 228); or 3) once-daily insulin glargine at the same time each day (IGlar OD; n = 230). The primary outcome was noninferiority of IDeg OD Flex to IGlar OD in HbA(1c) reduction after 26 weeks.RESULTSAfter 26 weeks, IDeg OD Flex, IDeg OD, and IGlar OD improved HbA(1c) by 1.28, 1.07, and 1.26% points, respectively (estimated treatment difference [IDeg OD Flex - IGlar OD]: 0.04% points [-0.12 to 0.20], confirming noninferiority). No statistically significant differences in overall or nocturnal hypoglycemia were found between IDeg OD Flex and IGlar OD. Comparable glycemic control and rates of hypoglycemia were seen with IDeg OD Flex and IDeg OD. Adverse event profiles were similar across groups.CONCLUSIONS
The use of extreme dosing intervals of 8-40 h demonstrates that the daily injection time of IDeg can be varied without compromising glycemic control or safety.
Diabetes care 01/2013; 36(4). DOI:10.2337/dc12-1668 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE
To compare ultra-long acting insulin degludec with glargine for efficacy and safety in insulin-naive patients with type 2 diabetes inadequately controlled with oral antidiabetic drugs (OADs).RESEARCH DESIGN AND METHODS
In this 1-year, parallel-group, randomized, open-label, treat-to-target trial, adults with type 2 diabetes with A1C of 7-10% taking OADs were randomized 3:1 to receive once daily degludec or glargine, both with metformin. Insulin was titrated to achieve prebreakfast plasma glucose (PG) of 3.9-4.9 mmol/L. The primary end point was confirmation of noninferiority of degludec to glargine in A1C reduction after 52 weeks in an intent-to-treat analysis.RESULTSIn all, 1,030 participants (mean age 59 years; baseline A1C 8.2%) were randomized (degludec 773, glargine 257). Reduction in A1C with degludec was similar (noninferior) to that with glargine (1.06 vs. 1.19%), with an estimated treatment difference of degludec to glargine of 0.09% (95% CI -0.04 to 0.22). Overall rates of confirmed hypoglycemia (PG <3.1 mmol/L or severe episodes requiring assistance) were similar, with degludec and glargine at 1.52 versus 1.85 episodes/patient-year of exposure (PYE). There were few episodes of nocturnal confirmed hypoglycemia in the overall population, and these occurred at a lower rate with degludec versus glargine (0.25 vs. 0.39 episodes/PYE; P = 0.038). Similar percentages of patients in both groups achieved A1C levels <7% without hypoglycemia. End-of-trial mean daily insulin doses were 0.59 and 0.60 units/kg for degludec and glargine, respectively. Adverse event rates were similar.CONCLUSION
Insulins degludec and glargine administered once daily in combination with OADs provided similar long-term glycemic control in insulin-naive patients with type 2 diabetes, with lower rates of nocturnal hypoglycemia with degludec.
Diabetes care 10/2012; 35(12). DOI:10.2337/dc12-1205 · 8.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: L’insuline dégludec (IDeg) est une insuline basale d’action ultra-longue avec un effet hypoglycémiant stable sur 24 h. Ceci permet de comparer l’IDeg en schéma flexible (IDeg Flex) à l’insuline glargine (IGlar) administrée à heure fixe.Patients et méthodesEssai contrôlé ouvert (26 semaines), chez des DT2 insulino-naifs (± ADO) randomisés (1:1) entre IDeg Flex (n = 229) X1/jour matin ou soir (minimum 8/maximum 40 heures entre 2 injections) et IGlar (n = 230) X1/jour à la même heure. Les deux insulines sont titrées pour une glycémie à jeun (GAJ) < 5 mmol/l. Les caractéristiques initiales des DT2 sont comparables entre groupes : âge (56,2 vs 56,7 ans), HbA1c (8,5 vs 8,4 %), GAJ (9,0 vs 9,0 mmol/l), durée du diabète (10,8 vs 10,8 ans), IMC (29,3 vs 30,0 kg/m2)Résultats88 % des patients/groupe terminent l’essai. À 26 semaines, IDeg Flex et IGlar diminue l’HbA1C de 1,28 et 1,26 % (IDeg Flex-IGlar : 0,04 % [IC 95 % : [−0,12; 0,20] La GAJ est significativement plus basse avec IDeg Flex (5,8 mmol/l) qu’avec IGlar (6,2 mmol/l) (IDeg Flex-IGlar : −0,42 mmol/l [−0,82; − 0,02] p = 0,04). Les doses moyennes d’insuline sont similaires entre les groupes. Les taux d’hypoglycémie (épisodes/année/patient) confirmée (glycémie < 3,1 mmol/l) ou sévère : 3,6 IDeg Flex vs 3,5 IGlar (RR IDeg Flex/IGlar : 1,03 [0,75; 1,40],) et les taux d’hypoglycémie nocturne : 0,6 IDeg Flex vs 0,8 IGlar; (RR : 0,77 [0,44; 1,35]) sont similaires entre groupes. (2 hypoglycémies sévères, même taux d’événements indésirables/groupe).Conclusion
Chez des DT2 insulino naifs, comparée à l’IGlar, l’IDeg peut être administrée une fois/jour selon un schéma flexible sans compromettre le contrôle glycémique ni la sécurité des patients. La GAJ sous IDeg Flex est significativement plus basse que sous IGlar sans augmentation du risque d’hypoglycémie nocturne.
[Show abstract][Hide abstract] ABSTRACT: The efficacy and safety of insulin degludec (degludec), a new-generation ultra-long-acting basal insulin, was compared with insulin glargine (glargine) in people with Type 1 diabetes mellitus in a 16-week, open-label, randomized trial. Health status, an important aspect of effective diabetes management, was also assessed.
Degludec (n = 59) or glargine (n = 59) were injected once daily, with insulin aspart at mealtimes. Health status assessment utilized the validated Short Form 36 Health Survey, version 2, which has two summary component scores for mental and physical well-being, each comprising four domains.
At study end, HbA(1c) reductions were comparable between groups, but confirmed nocturnal hypoglycaemia was significantly less frequent with degludec [relative rate 0.42 (95% CI 0.25-0.69)], and overall hypoglycaemia numerically less frequent [relative rate 0.72 (95% CI 0.52-1.00)]. After 16 weeks, a significant improvement in Short Form 36 Health Survey mental component score of +3.01 (95% CI 0.32-5.70) was obtained for degludec against glargine, attributable to significant differences in the social functioning [+8.04 (95% CI 1.89-14.18)] and mental health domains [+2.46 (95% CI 0.10-4.82)]. For mental component score, Cohen's effect size was 0.42, indicating a small-to-medium clinically meaningful difference. The physical component score [+0.66 (95% CI -2.30 to 3.62)] and remaining domains were not significantly different between degludec and glargine. ConCLUSIONS: In the context of comparable overall glycaemic control with glargine, degludec improved mental well-being as measured using the mental component score of the Short Form 36 Health Survey. The improvements in overall mental component score and the underlying social functioning and mental health domains with degludec compared with glargine may relate to the observed reduction in hypoglycaemic events.
Diabetic Medicine 12/2011; 29(6):716-20. DOI:10.1111/j.1464-5491.2011.03547.x · 3.12 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Insulin degludec is a new basal insulin that forms soluble multihexamer assemblies after subcutaneous injection, resulting in an ultra-long action profile. This study aimed to assess efficacy and safety of insulin degludec injected once a day or three times a week compared with insulin glargine once a day in insulin-naive people with type 2 diabetes, who were inadequately controlled with oral antidiabetic drugs.
In this 16-week, randomised, open-label, parallel-group phase 2 trial, participants aged 18–75 years with type 2 diabetes and glycosylated haemoglobin (HbA(1C)) of 7·0–11·0% were enrolled and treated at 28 clinical sites in Canada, India, South Africa, and the USA. Participants were randomly allocated in a 1:1:1:1 ratio by computer-generated block randomisation to receive insulin degludec either once a day or three times a week or insulin glargine once a day, all in combination with metformin. Investigators were masked to data until database release. The primary outcome was HbA(1C) after 16 weeks of treatment. Analyses were done by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00611884.
Of 367 patients screened, 245 were eligible for inclusion. 62 participants were randomly allocated to receive insulin degludec three times a week (starting dose 20 U per injection [1 U=9 nmol]), 60 to receive insulin degludec once a day (starting dose 10 U [1 U=6 nmol]; group A), 61 to receive insulin degludec once a day (starting dose 10 U [1 U=9 nmol]; group B), and 62 to receive insulin glargine (starting dose 10 U [1 U=6 nmol]) once a day. At study end, mean HbA(1C) levels were much the same across treatment groups, at 7·3% (SD 1·1), 7·4% (1·0), 7·5% (1·1), and 7·2% (0·9), respectively. Estimated mean HbA(1C) treatment differences from insulin degludec by comparison with insulin glargine were 0·08% (95% CI –0·23 to 0·40) for the three dose per week schedule, 0·17% (–0·15 to 0·48) for group A, and 0·28% (–0·04 to 0·59) for group B. Few participants had hypoglycaemia and the number of adverse events was much the same across groups, with no apparent treatment-specific pattern.
Insulin degludec provides comparable glycaemic control to insulin glargine without additional adverse events and might reduce dosing frequency due to its ultra-long action profile.
The Lancet 03/2011; 377(9769):924-31. DOI:10.1016/S0140-6736(10)62305-7 · 45.22 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to demonstrate differential effects of growth hormone (GH) on food intake in lean and obese rats and to investigate whether an anticipated anorectic response in obese rats might be associated with increased lipid oxidation and altered hypothalamic neuropeptide levels. GH (4 mg/kg/day) was administered during 5-21 days to non-obese and obese rats. Whereas GH stimulated food intake in the non-obese rats, the obese animals responded with a significantly (p<0.05) suppressed food intake for 4-5 days. On day 4, the obese rats injected with GH and those injected with vehicle consumed 9.2 ± 0.66 g and 12.7 ± 1.05 g, respectively. The suppression of food intake was associated with significantly (p<0.05) increased lipid oxidation. A similar, but statistically not verified, trend was seen in pair-fed rats not exposed to GH. However, while these animals appeared to economize their energy expenditure, the GH-exposed animals did not, thus creating a significant (p<0.05) difference between these two groups. The increased lipid oxidation and energy expenditure observed in the rats exposed to GH were associated with significantly (p<0.05) decreased levels of hypothalamic galanin (111 ± 33.2 pmol/g vs. those of the pair-fed controls: 228.5 ± 49.4 pmol/g). This difference was, however, not sustained. Thus, on day 21 both hypothalamic galanin and the food intake in the GH group were back to normal. Hypothalamic NPY remained unchanged by GH at all times. In conclusion, the present study suggests that increased lipid oxidation and decreased hypothalamic galanin are components in the mechanism by which GH inhibits food intake in an obese phenotype.
[Show abstract][Hide abstract] ABSTRACT: Introduction
L’insuline Degludec (IDeg) est un nouvel analogue de l’insuline qui forme des multi-hexamères solubles après injection sous-cutanée (SC), ce qui confère ainsi une durée d’action ultra longue.
Matériels et méthodes
Essai ouvert de phase 2, Treat to Target, de 16 semaines, randomisé en groupes parallèles, portant sur l’efficacité et l’innocuité de l’IDeg administrée le soir une fois par jour (1x/j), ou 3 fois par semaine (3S) chez des patients diabétiques de type 2, naïfs en insuline et non contrôlés par les antidiabétiques oraux (objectif de glycémie à jeun à 0,72 – 1,08 g/l).
Les patients (54,2 ans, HbA1c 8,7 %, GAJ 1,84 g/l, IMC 29,5 kg/m2) ont reçu l’IDeg 1x/j (n = 60), 3S (n = 62), ou de l’insuline Glargine 1x/j (IGlar, n = 62) plus metformine. Après 16 semaines de traitement, l’HbA1c était comparable en termes de diminution (IDeg 1x/j – 1,3 % ; IDeg 3S – 1,5 %, IGlar – 1,5 %) et de valeur obtenue (7,4 % ; 7,3 % et 7,2 %). La GAJ moyenne était aussi comparable en valeur obtenue (1,13 g/l, 1,16 g/l, et 1,15 g/l) et en réduction moyenne (− 0,65 g/l ; − 0,75 g/l et − 0,61 g/l). La dose d’insuline était similaire (3,1 U/kg/sem = 0,45 U/kg/jour, 3,4 U/kg/sem = 0,49 U/kg/jour et 3,3 U/kg/sem = 0,48 U/kg/jour). Le taux d’hypoglycémie confirmée était faible et semblait plus bas avec IDeg 1x/j qu’avec IDeg 3S et IGlar (0,6, 2,3 et 1,1 év/pt-année ; NS pour les deux). La proportion de sujets présentant des événements indésirables était voisine dans les 3 groupes (47 %, 50 % et 66 %).
L’IDeg utilisée 3 fois par semaine ou une fois par jour était bien tolérée et fournissait un contrôle glycémique similaire à l’IGlar.
[Show abstract][Hide abstract] ABSTRACT: Insulin degludec (IDeg) is a basal insulin that forms soluble multihexamers after subcutaneous injection, resulting in an ultra-long action profile. We assessed the efficacy and safety of IDeg formulations administered once daily in combination with mealtime insulin aspart in people with type 1 diabetes.
In this 16-week, randomized, open-label trial, participants (mean: 45.8 years old, A1C 8.4%, fasting plasma glucose [FPG] 9.9 mmol/L, BMI 26.9 kg/m(2)) received subcutaneous injections of IDeg(A) (600 μmol/L; n = 59), IDeg(B) (900 μmol/L; n = 60), or insulin glargine (IGlar; n = 59), all given once daily in the evening. Insulin aspart was administered at mealtimes. RESULTS At 16 weeks, mean A1C was comparable for IDeg(A) (7.8 ± 0.8%), IDeg(B) (8.0 ± 1.0%), and IGlar (7.6 ± 0.8%), as was FPG (8.3 ± 4.0, 8.3 ± 2.8, and 8.9 ± 3.5 mmol/L, respectively). Estimated mean rates of confirmed hypoglycemia were 28% lower for IDeg(A) compared with IGlar (rate ratio [RR]: 0.72 [95% CI 0.52-1.00]) and 10% lower for IDeg(B) compared with IGlar (RR: 0.90 [0.65-1.24]); rates of nocturnal hypoglycemia were 58% lower for IDeg(A) (RR: 0.42 [0.25-0.69]) and 29% lower for IDeg(B) (RR: 0.71 [0.44-1.16]). Mean total daily insulin dose was similar to baseline. The frequency and pattern of adverse events was similar between insulin treatments.
In this clinical exploratory phase 2 trial in people with type 1 diabetes, IDeg is safe and well tolerated and provides comparable glycemic control to IGlar at similar doses, with reduced rates of hypoglycemia.
Diabetes care 02/2011; 34(3):661-5. DOI:10.2337/dc10-1925 · 8.42 Impact Factor