100 years on: The impact of the discovery of insulin on clinical outcomes

Throughout history, up to the early part of the 20th century, diabetes has been a devastating disorder, particularly when diagnosed in childhood when it was usually fatal. Consequently, the successful pancreatic extraction of insulin in 1921 was a miraculous, life-changing advance. In this review, the truly transformative effect that insulin has had on the lives of people with type 1 diabetes and on those with type 2 diabetes who are also dependent on insulin is described, from the time of its first successful use to the present day. We have highlighted in turn how each of the many facets of improvements over the last century, from advancements in the properties of insulin and its formulations to the evolution of different methods of delivery, have led to continued improvement in clinical outcomes, through the use of illustrative stories from history and from our own clinical experiences. This review concludes with a brief look at the current challenges and where the next century of technological innovation in insulin therapy may take us

Lower rates of hypoglycaemia in older individuals with type 2 diabetes using insulin degludec versus insulin glargine U100 : results from SWITCH 2

Aim This study aimed to investigate the safety of insulin degludec (degludec) in relation to age and risk of hypoglycaemia post hoc in individuals with type 2 diabetes (T2D) (SWITCH 2 trial). Methods In this crossover study, individuals with T2D who were at risk of hypoglycaemia were randomized to double‐blind treatment with degludec or insulin glargine 100 units/mL (glargine U100) ± oral antidiabetic drugs. After 32 weeks, patients crossed over to the other treatment. Primary endpoint was number of overall severe (positively adjudicated) or glucose‐confirmed (plasma glucose <56 mg/dL; 3.1 mmol/L) symptomatic hypoglycaemia events during the two 16‐week maintenance periods. Results For individuals ≤65 (n = 450) and >65 (n = 270) years, baseline median (range) duration of diabetes was 12 (1–40) vs 15 (1–54) years, mean HbA1c was 7.7% vs 7.4% and mean estimated glomerular filtration rate was 87.0 vs 63.7 mL/min/1.73 m2, respectively. No significant differences in HbA1c reduction were seen in individuals ≤65 or >65 years. During both maintenance periods, treatment with degludec lowered rates of hypoglycaemia (overall/nocturnal symptomatic) vs those with glargine U100 in individuals ≤65 (31% vs 43%) and >65 (30% vs 41%) years. With degludec and glargine U100, respectively, six vs nine severe hypoglycaemic events occurred in individuals ≤65 years and four vs eight events occurred in those >65 years. Adverse event rates were 3.2 and 3.3 events/patient‐year for individuals ≤65 years and were 3.5 and 4.1 events/patient‐year for individuals >65 years with degludec and glargine U100, respectively. Conclusion Treatment with degludec was safe and effective, with a frequency of hypoglycaemia lower than that with glargine U100 in both younger and older individuals (>65 years) with T2D

A comparison of treatment with metformin and gliclazide in patients with non-insulin dependent diabetes

Twenty-seven obese non-insulin-dependent diabetic patients, treated with dietary carbohydrate restriction and metformin, were recruited from the diabetic outpatient clinic and entered into an open crossover study with gliclazide. Twenty-one patients completed the study. During three months observation on metformin, the mean weight of the group fell by 1.0 kg with 14 patients losing a mean of 1.8 kg with 14 patients losing a mean of 1.8 kg, 3 remaining unchanged and 4 gaining a mean weight of 1.1 kg. Over the subsequent three months on gliclazide, the mean weight of the group rose by 1.4 kg with 16 patients gaining a mean of 2.2 kg, two remaining unchanged and 3 losing a mean of 2.0 kg. In addition, 10 patients were heavier after gliclazide than at the time of recruitment (mean 2.6 kg), 3 were unchanged and 8 had lost weight since commencing the trial (mean 2.1 kg), mostly due to greater loss on metformin than gain on gliclazide. Glycaemic control did not improve significantly during the observed period on metformin but lower concentrations of fasting glucose and total glycosylated haemoglobin were achieved with gliclazide. Mean plasma insulin concentration was significantly higher and mean serum lactate was significantly lower during treatment with gliclazide. In conclusion, gliclazide does not support weight loss in obese non-insulin-dependent diabetic patients to the same extent as metformin but the difference between the two drugs is small. Gliclazide is a suitable oral hypoglycaemic agent for use in the obese diabetic who cannot be controlled by diet alone

Incidence and severity of hypoglycaemia in type 2 diabetes by treatment regimen: a UK multi-site 12-month prospective observational study

Aims To determine the incidence and severity of self‐reported hypoglycaemia in a primary care population with type 2 diabetes. The study also aimed to compare incidence by treatment regimen. Materials and methods A prospective observational study in 17 centres throughout the UK was conducted. Recruitment was based on treatment regimen (metformin alone, sulphonylurea‐, insulin‐ or incretin‐based therapy). Participants were asked to keep a blood glucose diary and self‐report hypoglycaemia episodes [non‐severe (self‐treated) and severe (requiring external help)] over a 12‐month period. Results Three hundred and twenty‐five participants were enrolled, of whom 274 (84%) returned ≥1 monthly diaries. Overall, 39% reported experiencing hypoglycaemia; 32% recorded ≥1 symptomatic, 36% ≥1 non‐severe, and 7% ≥1 severe episodes. By treatment, incidence (events per person/year) for any hypoglycaemia type was 4.39 for insulin, 2.34 for sulphonylurea, 0.76 for metformin, and 0.56 for incretin‐based therapy. Compared with metformin, risk of non‐severe hypoglycaemia was ~3 times higher for participants on sulphonylureas and > 5 times higher for those on insulin [incidence rate ratio (IRR) 3.02 (1.76‐5.18), P < 0.001, and IRR 5.96 (3.48‐10.2), P < 0.001, respectively]. For severe episodes, the incidence for sulphonylurea (0.09) was similar to metformin (0.07) and incretin‐based therapy (0.07); for insulin the risk remained almost 5 times higher than metformin [incidence 0.32; IRR 4.55 (1.28‐16.20), P = 0.019]. Conclusions Hypoglycaemia represents a substantial burden for people with type 2 diabetes. Sulphonylureas and insulin are both associated with a risk of reported non‐severe hypoglycaemia, but only insulin with severe episodes. This suggests the importance of the continued use of sulphonylureas in appropriate patients with type 2 diabetes