Curr Med Res Opin. 2016 Sep;32(9):1557-65.

Outcomes and healthcare resource utilization associated with medically attended hypoglycaemia in older patients with type 2 diabetes initiating basal insulin in a US managed care setting

Javier Escaladaa, Laura Liaob, Chunshen Panc, Hongwei Wangb and Mohan Balad

aDepartment of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain; bSanofi, Bridgewater, NJ, USA; cPro Unlimited, Boca Raton, FL, USA; dSanofi, Cambridge, MA, USA



Objective: To assess health outcomes and the economic burden of hypoglycaemia in older patients with type 2 diabetes initiating basal insulin (BI).

Research design and methods: Medicare Advantage claims data were extracted for patients with type 2 diabetes initiating BI and patients were stratified into two groups: those with medically attended hypoglycaemia during the first year of BI treatment (HG group) and those without (non-HG group).

Main outcome measures: Hospitalisation, mortality, healthcare utilisation and costs 1 year before and 1 year after BI initiation.

Results: Of 31,035 patients included (mean age 72 years [SD 9.2]), 3,066 (9.9%; HG group) experienced hypoglycaemia during 1 year post-BI initiation. Hypoglycaemia was an independent risk factor for hospitalisation (HR 1.59; 95% CI: 1.53–1.65) and death (HR 1.50; 95% CI: 1.40–1.60). Healthcare utilisation was higher pre-index, and showed greater increases post-BI initiation, in the HG vs the non-HG group. Per-patient healthcare costs were substantially higher for the HG group than the non-HG group, both pre-index ($54,057 vs $30,249, respectively) and post-BI initiation ($75,398 vs $27,753, respectively).

Conclusions: Hypoglycaemia during the first year of BI treatment heightens the risk of hospitalisation or death in older people, increasing healthcare utilisation and costs. Insulin regimens with a lower risk of hypoglycaemia may ameliorate these issues.



Older patients represent the fastest growing diabetes population in the US and globally.1,2 For those diagnosed with type 2 diabetes, many will ultimately progress to requiring insulin therapy.3 Effective insulin treatment must strike a fine balance between the lowering of blood glucose levels to prevent the complications of hyperglycaemia and the avoidance of hypoglycaemic episodes. Older patients are particularly vulnerable to hypoglycaemia due to high levels of comorbidity, competing disease management regimens and overall frailty.4 Due to their often poor health status, many older patients with comorbid conditions are excluded from clinical trial participation. It is, therefore, important to analyse the outcomes of diabetes treatment of older patients in real-world settings to fully appraise the effectiveness of currently available therapeutic agents.

In our study, we evaluated the effect of medically attended hypoglycaemia (i.e. severe hypoglycaemia) on older patients with type 2 diabetes in the US (mean age 72 years; standard deviation [SD] 9.2) in terms of healthcare resource utilisation, treatment costs and mortality rates. Medical claims data were extracted for an insulin-naïve population who initiated basal insulin treatment over a five-year period (N=31,035). Patients were followed from 12 months prior to a first prescription for basal insulin (index date) and for at least 12 months of insulin therapy (Figure 1).



Figure 1. Study design

A total of 3,066 (9.9%) patients required medical assistance for hypoglycaemia in the first year after initiating basal insulin treatment, experiencing a mean number of 4.5 events each. After adjusting for demographic, comorbidity and medication history, a previous experience of severe hypoglycaemia increased the subsequent likelihood of a patient being admitted to hospital (hazard ratio [HR] 1.59; 95% confidence interval [CI]: 1.53–1.65) or to die (HR 1.50; 95% CI: 1.40–1.60) compared with those who did not experience hypoglycaemia (Figure 2).


Figure 2. Mortality rates following initiation of basal insulin, by hypoglycaemia status


It was postulated that patients with comorbidities might be predisposed to hypoglycaemia, and that these comorbidities may underlie the higher mortality seen in patients who experienced hypoglycaemia. Indeed, patients who experienced hypoglycaemia had a higher comorbidity level before starting basal insulin and showed a substantial increase in microvascular and macrovascular complications following basal insulin initiation, compared with stable levels of comorbidity in those patients not experiencing hypoglycaemia. However, in a sensitivity analysis of a population at risk of cardiovascular events (which included only patients with myocardial infarction, congestive heart failure, peripheral vascular disease or stroke), patients who experienced hypoglycaemia remained at increased risk of death compared to those without hyperglycaemia (HR 1.46; 95% CI: 1.34–1.58). Our findings reveal a more complex interplay between hypoglycaemia and mortality beyond hypoglycaemia acting as a marker of increased cardiovascular risk and mortality.

The impact of the impaired health outcomes observed for patients experiencing hypoglycaemia is brought into sharp focus when considering healthcare costs. Prior to starting basal insulin treatment, the patient group that went on to experience hypoglycaemia were already 79% more costly to treat than those without hypoglycaemia (annual cost $54,057 vs $30,249, respectively, p<0.001) and these annual costs increased by 39% to $75,398 following basal insulin initiation (of which hypoglycaemia-related costs contributed $5,337 [7%]), compared with stable costs in the population without hypoglycaemia. These costs were reflected in the observed patterns of healthcare utilisation: patients with hypoglycaemia were more often hospitalised, taken to the emergency room or seen at a clinician’s office versus those without hypoglycaemia, an observation that is likely to be linked to the differential comorbidity levels in these two groups.

Our analysis highlights an association between severe hypoglycaemia and subsequent risk of hospitalisation and death in older patients with type 2 diabetes initiating basal insulin. Reducing the hypoglycaemia risk of insulin treatment, either through new agents or by optimising combination therapy, is a desirable health outcome that may alleviate the medical and economic burden of diabetes care in this fragile older population.



  1. Cheng YJ, Imperatore G, Geiss LS, et al. Secular changes in the age-specific prevalence of diabetes among U.S. adults: 1988-2010. Diabetes Care 2013;36:2690-96.
  2. International Diabetes Federation. Diabetes Atlas 2015; Seventh Edition. Available at: (accessed 18 January 2017)
  3. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes: a patient-centered approach: position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2012;35:1364-79.
  4. Miller ME, Williamson JD, Gerstein HC, et al. Effects of randomization to intensive glucose control on adverse events, cardiovascular disease, and mortality in older versus younger adults in the ACCORD Trial. Diabetes Care 2014;37:634-43.



Declaration of funding This study and editorial assistance in the preparation of this paper were funded by Sanofi. J.E. interpreted the data and critically reviewed the manuscript. L.L. critically reviewed the manuscript, C.P. researched the data and performed the data analysis. H.W. designed the study and critically reviewed the manuscript. M.B. contributed to the discussion and critically reviewed the manuscript. Professor Javier Escalada is the guarantor of this work and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Declaration of financial/other relationships J.E. has disclosed that he has served on advisory panels for MSD and Sanofi, and has participated in speaker’s bureaus for Astra-Zeneca, Boehringer/Lilly, MSD and Sanofi. H.W. and M.B. have disclosed that they are employees of Sanofi. C.P. has disclosed that she has acted as a consultant to Sanofi. L.L. has disclosed that she was an employee of Sanofi at the time of the study.

Acknowledgments Editorial assistance was provided by Julianna Solomons of Fishawack Communications Ltd., funded by Sanofi.

Previous presentation Aspects of this study have been presented as a poster presentation at the American Diabetes Association 75th Scientific Sessions, 5–9 June 2015, Boston, United States; and at the 51st European Association for the Study of Diabetes Annual Meeting, 14–18 September 2015, Stockholm, Sweden.

Manuscript in full: Javier Escalada, Laura Liao, Chunshen Pan, Hongwei Wang & Mohan Bala. Outcomes and healthcare resource utilization associated with medically attended hypoglycemia in older patients with type 2 diabetes initiating basal insulin in a US managed care setting. Current Medical Research and Opinion 2016. DOI:10.1080/03007995.2016.1189893



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