ment satisfaction and QOL in 366 patients randomized to
insulin glargine vs adjusted OADs.12 Perceived frequency
of hypoglycemia was no different between both groups at
the end of 24 weeks. The QOL improved in both groups
but was greater in the glargine group throughout the
study. The A1c reduction was also greater in the insulin
glargine arm. This study highlighted the positive social-psychological impact of early insulin therapy without significant hypoglycemia and its effects.20
The metabolic benefits of early insulin therapy are demonstrated in multiple trials, but the data are difficult to interpret. Providers agree the goal in diabetes management
is both to delay b-cell failure and prevent the often irreversible metabolic damage from chronic hyperglycemia.
The inability to achieve this goal can be due to delayed insulin therapy. For those with A1c ≤ 8% the data to support
earlier insulin therapy require the physician to look more
at the metabolic benefits of insulin rather than just A1c reduction.
For patients with A1c ≥ 8%, or for those with multiple comorbidities needing rapid glucose improvement
with additional secondary metabolic benefit, earlier insulin therapy may be practical. Ultimately it is left to
the patient and provider to determine the best pharmacotherapy based on personal preference, risk for macro/
microvascular complications, and AEs (Table). This will
require evidence-based decision making in the setting
of a personalized diabetes treatment plan.
1. Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2014.
Centers for Disease Control and Prevention Website. http://www.cdc.gov/diabetes
/pubs/ statsreport14.htm. Updated July 29, 2014. Accessed September 16, 2014.
2. Garber AJ, Abrahamson MJ, Barzilay JI, et al; American Association of Clinical
Endocrinologists. AACE comprehensive diabetes management algorithm 2013.
Endocr Pract. 2013;19(2):327-336.
3. Kahn SE, Haffner SM, Heise MA, et al; ADOPT Study Group. Glycemic durability of rosiglitazone, metformin or glyburide monotherapy. N Engl J Med.
4. Intensive blood-glucose control with sulphonylureas or insulin compared with
conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet.
5. Owens DR. Clinical evidence for the earlier initiation of insulin therapy in type 2
diabetes. Diabetes Technol Ther. 2013;15(9):776-785.
6. Diamant M. Choosing a blood-glucose-lowering agent after metformin. Lancet.
7. Bailey T. Options for combination therapy in type 2 diabetes: Comparison of the
ADA/EASD position statement and AACE/ACE algorithm. Is J Med. 2013;126(9
8. Pistrosch F, Köhler C, Schaper F, Landgraf W, Forst T, Hanefeld M. Effects of insulin glargine versus metformin on glycemic variability, microvascular and beta-cell
function in early type 2 diabetes. Acta Diabetol. 2013;50(4):587-595.
9. Gerstein HC, Miller ME, Byington RP, et al; Action to Control Cardiovascular Risk
in Diabetes Study Group. Effects of intensive glucose lowering in type 2 diabetes.
N Engl J Med. 2008;358(24):2545-2559.
10. Patel A, MacMahon S, Chalmers J, et al; ADVANCE Collaborative Group. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes.
N Engl J Med. 2008;358(24):2560-2572.
11. Duckworth W, Abraira C, Moritz T, et al; VADT Investigators. Glucose control and vascular complications in veterans with type 2 diabetes. N Engl J Med
12. Gerstein HC, Yale JF, Harris SB, Issa M, Stewart JA, Dempsey E. A randomized trial
of adding insulin glargine vs avoidance of insulin in people with type 2 diabetes on
either no oral glucose-lowering agents or submaximal doses of metformin and/or
sulphonylureas. The Canadian INSIGHT (Implementing New Strategies with Insulin Glargine for Hyperglycaemia Treatment) Study. Diabet Med. 2006;23(7):736-742.
13. Mellbin LG, Rydén L, Riddle MC, et al; ORIGIN Trial Investigators. Does hypoglycemia increase the risk of cardiovascular events? A report from the ORIGIN trial.
Eur Heart J. 2013;34(40):3137-3144.
14. ORIGIN Trial Investigators. Characteristics associated with maintenance of mean
A1C < 6.5% in people with dysglycemia in the ORIGIN trial. Diabetes Care.
15. Gerstein HC, Bosch J, Dagenais GR, et al; ORIGIN Trial Investigators. Basal
insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med.
16. Weng J, Li Y, Xu W, et al. Effect of intensive insulin therapy on beta-cell function
and glycaemic control in patients with newly diagnosed type 2 diabetes: A multicentre randomised parallel-group trial. Lancet. 2008;371(9626):1753-1760.
17. Roumie CL, Greevy RA, Grijalva CG, et al. Association between intensification of
metformin treatment with insulin vs sulfonylureas and cardiovascular events and
all-cause mortality among patients with diabetes. JAMA. 2014;311(22):2288-2296.
18. Aschner P, Chan J, Owens DR, et al; EASIE Investigators. Insulin glargine versus sitagliptin in insulin-naive patients with type 2 diabetes mellitus uncontrolled on metformin (EASIE): A multicentre, randomised open-label trial. Lancet.
19. Zoungas S, Patel A, Chalmers J, et al; ADVANCE Collaborative Group. Severe hypoglycemia and risks of vascular events and death. N Engl J Med.
20. Houlden R, Ross S, Harris S, Yale JF, Sauriol L, Gerstein HC. Treatment satisfaction and quality of life using early insulinization strategy with insulin glargine
compared to an adjusted oral therapy in the management of type 2 diabetes: The
Canadian INSIGHT study. Diabetes Res Clin Pract. 2007;78(2):254-258.
Table. Pros and Cons of Early Initiation of
Rapid glycemic control Hypoglycemia (minor and
Preserve ß-cell function Weight gain
Anti-inflammatory effect Increase cardiovascular risk
Antioxidant effect Perceived burden of care
risk (population depen-
Improvement in quality