CHAPTER 5. Clinical Guideline for Pharmacological Management of Adults With Type 2 Diabetes

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Evidence-Based Diabetes Management, June 2018, Volume 24, Issue 7

From the Adult Diabetes and Clinical Research Sections, Joslin Diabetes Center, Harvard Medical School. Approved May 10, 2016; updated April 24, 2018. For the Figure and Tables, download the PDF at the end of the chapter.

Objective: The objective of the Joslin Diabetes Center Clinical Guideline for Pharmacological Management of Adults with Type 2 Diabetes is to support clinical practice, influence clinical behavior to improve outcomes, and to assure quality of care according to accepted standards. The guideline was established after careful review of current evidence, literature, and clinical practice. This guideline is reviewed periodically and modified to reflect changes in clinical practice and available pharmacological information.


This guideline is not intended to serve as a mandatory standard, but rather to provide a set of recommendations for patient care management. These recommendations are not a substitute for sound and reasonable clinical judgment or decision making and do not exclude other options. Clinical care must be individualized to the specific needs of each patient and interventions must be tailored accordingly. The guideline has been created to address initial presentations and treatment strategies in the adult nonpregnant patient population. The guideline is not a substitution for full prescribing information. Refer to Joslin’s Clinical Guideline for Adults with Diabetes (Chapter 1) as well as Joslin’s Guideline for the Care of Older Adults With Diabetes (Chapter 4) for additional, more comprehensive information on diabetes care and management.

  • Random plasma glucose (PG) ≥200 mg/dl and symptoms of diabetes (polyuria, polydipsia, ketoacidosis, or unexplained weight loss) or
  • Glycated hemoglobin (A1C) ≥6.5%a or
  • Fasting plasma glucoseb ≥126 mg/dl or
  • Results of a 2-hour 75-g oral glucose tolerance test ≥200 mg/dL at 2 hours

aOnly an A1C test that has been referenced to an accepted laboratory method (standardized) should be utilized for diagnostic purposes. Consider evaluation for hemoglobin variant if A1C is discordant from PG values.



5.3.1 Advancing antidiabetes medications:

bThese tests should be confirmed by a repeat test, on a different day, unless unequivocally high.


5.4.1 First-line add-on to metformin or use as monotherapy if metformin is contraindicated: see table SP256


TABLE 3. Preferred Considerations in Patients With T2D and Established Cardiovascular Disease


5.6.1 Examples of fixed-dose medications: (Table 4)



5.8.1 Premixed insulin combinations:

TABLE 2. Considerations for Selecting Noninsulin Glucose-Lowering MedicationsTABLE 7. Premixed Insulin Combinations

Notes for Figure and Tables

  1. Goals should be individualized based on factors that include the following: comorbidities, age, duration of diabetes, hypoglycemic awareness.
  2. If diet history reveals markedly excessive carbohydrate intake, consider initial trial of nutrition therapy and physical activity before initiating oral antidiabetes medications, even if glucose levels are above thethresholds listed.
  3. Some patients with T2D initially stabilized on insulin may be considered for transition to noninsulin antidiabetes medications as blood glucose control permits.
  4. May need to taper and discontinue some or all oral antidiabetes medications as insulin is initiated and adjusted, particularly if using short- or rapid-acting and basal insulins.
  5. Pre- and postprandial blood glucose should be checked. Frequency of checking may vary; it can be 1 to 4 times/day depending on individual patient and status of glycemic control.
  6. There is an increased risk for edema when insulin and a thiazoli-dinedione are used together. Rosiglitazone should not be used in combination with insulin.
  7. FDA requirements for LFT monitoring for thiazolidinediones (TZDs): If initial alanine aminotransferase (ALT) is >2.5 times normal, do not start this medication. If ALT is >2.5 times normal during treatment, check weekly. If rise persists or becomes >3 times normal, discontinue TZD.
  8. Thiazolidinediones cause or exacerbate congestive heart failure in some patients. After initiation of TZDs and after dose increases, observe patients carefully for signs and symptoms of heart failure (including excessive or rapid weight gain; dyspnea; and/or edema). If these signs and symptoms develop, the heart failure should be managed according to current standards of care. Furthermore, discontinuation or dose reduction of the TZD must be considered. TZDs are not recommended in patients with symptomatic heart failure or in patients with established NYHA Class III or IV heart failure.
  9. a. On September 23, 2010, the FDA announced regulatory actions with respect to products containing rosiglitazone: Avandia (rosiglitazone maleate) tablets, Avandamet (rosiglitazone maleate and metformin hydrochloride) tablets, and Avandaryl (rosiglitazone maleate and glimepiride) tablets. These FDA actions required GlaxoSmithKline to implement restrictions on the use of these products through a Risk Evaluation and Mitigation Strategy (REMS) program to assure their safe use and through additional safety labeling changes in responseto the agency’s review of data that suggested an elevated risk ofcardiovascular events. However, based on additional data review, the REMS program was removed as of December 16, 2015. Rosiglitazone now has the same indications for prescribing as pioglitazone.

9.b. According to the FDA advisory issued on June 15, 2011, regarding potential increased risk of bladder cancer with pioglitazone use: (1) Do not use pioglitazone in patients with active bladder cancer. (2) Use pioglitazone with caution in patients with a prior history of bladder cancer. The benefits of glycemic control versus unknown risks for cancer recurrence with pioglitazone should be considered in patients with a prior history of bladder cancer.

10. Risks of acute pancreatitis or pancreatic cancer have not been confirmed in clinical trials. The FDA is currently monitoring clinical reports via the Adverse Event Reporting System.

11. Diabetic ketoacidosis (DKA) with SGLT-2 inhibitors: Rare but sometimes serious cases have been reported. Check for DKA if symptomsdevelop, even if glucose levels are not elevated.

12. The potential benefits of SGLT-2 inhibitors in preventing progression of early renal disease are being investigated.



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