Deintensification Discourse: Why are we still hesitant to pump the breaks on diabetes management?

It is well-established that the efficacy of diabetes therapy is frequently limited by clinical inertia, whether it be attributed to the patient, the clinician, or the health care system. The need for more frequent follow-up and education in the management of diabetes mellitus has created an area of opportunity for pharmacists, as we are more available to meet with patients and facilitate the initiation and acceleration of different therapies. Yet, we are often so concerned with adding on antihyperglycemic agents to getting our patients to goal that we often forget to pause and reassess if the patient really needs all of the medication they are prescribed.

In 2012, the American Diabetes Association (ADA) and European Association for the Study of Diabetes dismissed the one-size-fits-all-approach for glycemic targets and released a position statement describing the importance of individualizing treatment strategies, with an emphasis on patient-centered care and shared decision-making in the management of patients with type 2 diabetes.(1) This was based on literature that demonstrated intensive glycemic control (A1c <6–6.5%) may improve surrogate outcomes for microvascular complications and reduce cardiovascular events at the possible expense of all-cause mortality.(2-5) Factors such as disease duration, life expectancy, comorbidities, established vascular complications, patient preferences, available resources and support, along with risk for hypoglycemia and other adverse effects should be taken into consideration when establishing patient-specific glycemic targets.(6) As clinicians, we frequently assess these factors at diagnosis, but do we do the same for our aging patients with long-standing diabetes?

While we may think this isn’t a common problem, multiple studies have demonstrated possible overtreatment in vulnerable populations (7) and poor rates of treatment deintensification among patients with low HbA1c values or those at risk for hypoglycemia.(8, 9) A retrospective cohort study of data from the Veterans Health Administration examined rates of treatment deintensification among patients that were aged 70 years or older on active treatment for diabetes.(8) Of the 23,769 patients with moderately low HbA1c levels (6.0–6.4%) and the 12,917 patients with very low HbA1c levels (<6%), treatment deintensification was initiated in 20.9 and 27.0% of patients, respectively. Another retrospective analysis using OptumInsight data from 2004 through 2010 determined that antihyperglycemic therapy was deintensified in 18.3% of all patients with recently diagnosed type 2 diabetes mellitus.(9) Furthermore, treatment deintensification occurred in only 19.4% of patients with multiple comorbidities and 21.2% of those that met authors’ definition for frailty, regardless of glycemic control at baseline. This demonstrates the need for us as clinicians to step back and think, “does my patient actually need all of this medication?”

The widespread lack of treatment deintensification described by these studies demonstrates the need for further education among health care professionals and stakeholders. Patients that have not yet experienced a hypoglycemic event and are comfortable with their diabetes treatment are often empowered by their glycemic control, and therefore, patient preference serves as a barrier to deintensification. Providers may struggle identifying the need for and prioritizing diabetes treatment deintensification because what appears to be well-controlled diabetes may seem like the smallest obstacle in the road to comprehensive disease management, especially when patients present with a list of more active problems that require immediate attention. So, how can we better recognize the patient-specific transition of well-controlled to overcontrolled diabetes? How often do you assess an A1c goal in a well-controlled patient and consider their risk of hypoglycemia and falls along with their comorbid conditions to incorporate those factors into their treatment plan?

Just as pharmacists have demonstrated value in the implementation and optimization of antihyperglycemic therapy, their role in identifying those that would benefit from treatment deintensification and facilitating that process is equally important. That being said, what are some strategies you have used to identify the need for and to initiate deintensification of therapy in clinical practice?

Authored by Liz Van Dril, PharmD, PGY-1 Resident, Midwestern University

  1. 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.
  2. Zoungas S, Chalmers J, Neal B, et al. Follow-up of blood-pressure lowering and glucose control in type 2 diabetes. N Engl J Med. 2014;371:1392–406.
  3. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545–59.
  4. Gerstein HC, Miller ME, Genuth S, et al. Long-term effects of intensive glucose lowering on cardiovascular outcomes. N Engl J Med. 2011;364:818–28.
  5. Hayward RA, Reaven PD, Wiitala WL, et al. Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2015;372:2197–206.
  6. Inzucchi SE, Bergenstal RM, Buse JB, et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care. 2015;38:140–149.
  7. Lipska KJ, Ross JS, Miao Y, et al. Potential overtreatment of diabetes mellitus in older adults with tight glycemic control. JAMA Intern Med. 2015;175:356–362.
  8. Sussman JB, Kerr EA, Saini SD, et al. Rates of deintensification of blood pressure and glycemic medication treatment based on levels of control and life expectancy in older patients with diabetes mellitus. JAMA Intern Med. 2015;175:1942–1949.
  9. McAlister FA, Youngson E, Eurich DT. Treatment deintensification is uncommon in adults with type 2 diabetes mellitus: a retrospective cohort study. Circ Cardiovasc Qual Outcomes. 2017;10(4).
  10. National Committee for Quality Assurance. Healthcare effectiveness data and information set: comprehensive diabetes care. (accessed 2017 June 11).


Treatment of T2DM after metformin: what’s next?

Pharmacologic options for the treatment of type 2 diabetes mellitus have expanded over the past ten years.  Metformin has remained the first-line agent due to a well-established safety and efficacy, low cost, and data demonstrating a reduction in cardiovascular events.1  It is pretty clear from a number of studies that metformin therapy should be maximized, which in some patients may require doses above 2000 mg/day. 2  Second-line treatments include a variety of agents, including basal insulin, dipeptidyl-peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT2) inhibitors, sulfonylureas, and thiazolidinediones.  Metformin is synergistic with many of the other agents, and should not be discontinued as beneficial effects can be seen even in patients taking insulin as the second line agent. 3 The 2016 treatment recommendations detail the above mentioned medications as all viable options for second-line therapy with no preference to one drug class over the other. 1 While this seems like this might open up treatment options for clinicians, it often in fact, leaves clinicians wondering about the BEST next option for their patients.  All of the options will always have a cost/benefit ratio, and so trying to choose the best agent that minimizes patient out of pocket costs is important.  In that regard, SGLT2s from all the current manufacturers have co-pay cards to minimize the cost (for patients not on Medicare).

The likely reason for no definitive recommendation for a second-line agent is that controversy exists regarding which agents should be used for the treatment of T2DM in those who cannot achieve glycemic control with metformin alone.  The newer agents, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors are effective, exhibit positive/neutral effects on body weight, and pose minimal risk of hypoglycemia in comparison to other available agents to treat hyperglycemia. Trials have been completed, or are ongoing, regarding the cardiovascular effects of these agents.3-9   and in the case of empagloflozin, the results of a recent trial have resulted in the manufacturer seeking a cardiovascular risk reduction, and leading to a debate on whether FDA should grant this request ( 5  Thus far, CV outcomes have either been positive or neutral with these agents leading clinicians to head towards those agents even though the cost may be higher.

Recently, the FDA has issued concerns regarding the newest agents, the SGLT2 inhibitors regarding the risk for acute kidney injury and ketoacidosis leaving us scratching our heads again, especially after some data exists that there many actually be reno-protection from this drug class (  Time and studies will tell which may be the best second line agents, but it is always important to consider patient out-of-pocket costs especially since diabetes patients take many different medications for diabetes, hypertension, and dyslipidemia…and more.



  1. American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2016;39(Suppl 1)
  2. Hirst JA, Farmer AJ, Ali R, et al. Quantifying the effect of metformin treatment and dose on glycemic control. Diabetes Care. 2012;35:446-454.
  3. Holden SE, Jenkins-Jones S, Currie CJ. (2016) Association between insulin monotherapy versus insuln plus metformin and the risk of all-cause mortality and other serious outcomes: a retrospective cohort study. PLoS ONE 11(5):e0153594. Doi:10.137/journal.pone.0153594.
  4. Pfeffer MA, Claggett B, Diaz R, et al. Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome. N Engl J Med. 2015 Dec 3;373(23):2247-57.
  5. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes. N Engl J Med 2015; 373:2117-2128.
  6. Scirica BM, Bhatt DL, Braunwald E, et al; for the SAVOR-TIMI 53 Steering Committee and Investigators. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med. 2013;369(14):1317-1326.
  7. White WB, Cannon CP, Heller SR, et al; for the EXAMINE Investigators. Alogliptin after acute coronary syndrome in patients with type 2 diabetes. N Engl J Med. 2013;369(14):1327-1335.
  8. Zannad F, Cannon CP, Cushman WC, et al; for the EXAMINE Investigators. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE:  a multicentre, randomised, double-blind trial. Lancet. 2015;385:2067-2076.
  9. Van der Werf F, Armstrong P. Trial evaluating cardiovascular outcomes with sitagliptin in patients with type 2 diabetes: TECOS. Presented at ESC Congress 2015. London, England, UK. Abstract 3147.