Medications

1. Introduction to diabetes medication classes

Drug classes differ by their mechanism of action, A1c lowering capacity, side effects, risk of hypoglycemia, effect on weight and vascular protection. Click the class headings below to review these and specific brand considerations. To view brand indications, doses and cost visit the Complete Diabetes Medication Table.

2. Questions to ask before medication changes

Prior to adjusting or adding more medications to address hyperglycemia, consider these.

• Variables impacting dosing suggestions:   
  Elements to consider prior to medication adjustment include the items below, as well as additional items in the small table of variables (link) and the big table of troubleshooting hypo and hyper (link). e.g. insulin integrity, lipohypertrophy, etc. 
  
  
• A1c:
  • How much does A1c need to change to reach individualized target? Or does it, e.g. frail with A1c 8.0%?
  • Will some drugs be more effective than others in getting A1c into target? 
• Safety or Benefits - Will new medication or dose impact:
  • Risk or reduction of hypoglycemia (commercial driver, frail elderly etc),
  • Complexity or simplification of the new regime (move to combo meds: med+med or insulin+med)
  • Comborbidities (benefits for CKD, HF, CVD, obesity or does dose need adjusting for CKD?)  
  • Risk of DKA (ability and willingness to test for ketones if increasing SGLT-2)
• Adherence: 
  • Will increased adherence impact glycemic control?
  • Can a simplified regimen with combination medications or once daily versions of medications improve adherence? If yes, are they affordable?   
• Lifestyle: 
  • Can lifestyle changes help to improve glycemia (e.g. what is duration of diabetes)? If adequate beta cell function remains in type 2 diabetes, lifestyle changes could potentially reduce A1c by 0.5-2.0% depending on the type and extent of the change.  Consider offering the Worksheet: Managing Blood Sugars.
• Current medication dose change:
  • Will adusting current medication likely bring them to target or is another agent also needed? E.g. if A1c 10%,  client on max metformin with near maximum gliclazide, consider an increase to the latter with a simultaneous request for another agent to be added. Maximum daily doses are outlined in our Complete Diabetes Medications Table.
  • Will adusting current medication address the blood glucose pattern
  • Are there factors that would suggest a more aggressive dose adjustment (prednisone, minimal effects of last adjustment, obesity)?
  • Are there factors that would suggest a more conservative dose adjustment?  (frail, low eGFR, inability to self-treat hypoglycemia, lean patient, anticipated rapid weight loss with bariatric surgery, planned significant dietary changes, planned increased exercise, history of severe hypoglycemia, fear of hypoglycemia, etc)?
  • What do you anticipate will happen to the glucose pattern after the medication adjustment? Are there safety concerns to address now or when readings drop to a certain level? Eg. Readings are in target except high at bed. An increase to supper repaglinide may require a reduction in overnight basal insulin.

3. Choosing next line agents

​The use of two medications from the same class is generally not indicated E.g. two secretagogues or 2 incretin-based medications (DPP-4 and GLP-1). To learn Health Canada indications and doses, visit the Drug Product Database or our Complete Diabetes Medications Table. 

A. Review Diabetes Canada Algorithms and/or use the tools in B. below. 

Figure 1: At Diagnosis of Type 2 Diabetes. Click image for bigger view.	Figure 2A: Reviewing, Adjusting or Advancing Therapy in type 2 diabetes. Click image for bigger view.	Figure 3: Starting or Advancing Insulin in Type 2 Diabetes. Click image for bigger view.
Source: Canadian Journal of Diabetes 2020 44575-591DOI: (10.1016/j.jcjd.2020.08.001)

B. Consider the Diabetes Canada's tool "Pharmacotherapy for Type 2 Diabetes" 
or the table of Diabetes Medications Class Benefits in the Topics Catalogue. Make decisions based on the most relevant features for your client:

• Relative A1c Lowering
• Hypoglycemia
• Renal benefits
• Heart failure hospitalization benefits
• Cardiovascular benefits
• Weight
• Other therapeutic considerations (safety of drug with comorbidities)
• Cost
• Pregnant or planning pregnancy
• Additional considerations: Patient preference  and adherence (consider once-daily/once weekly dosing if adherence is a concern) 

C. Consider Renal Impairment:

• Diabetes Canada Renal Dosing Chart (click chart to enlarge)

4. Drug Interactions

Patients should review potential drug interactions or side effects with pharmacists when starting any medication. Educators can review interactions in product monographs via Canada's Drug Product Database. A few interactions that impact glycemia are listed below. 

Hypoglycemia risk increases with:

• Beta blockers – may decrease symptoms of lows
• Salicylates/NSAIDs – if 4-6 g/day or greater
• Antibiotics: Fluoroquinolones (e.g. ciprofloxacin) can stimulate beta cells to secrete insulin. Hypoglycemia has been reported in patients without diabetes and in patients with diabetes on any antihyperglycemic agent, especially those on insulin or secretagogues.

Hyperglycemia risk increases with:

• Glucocorticoids- including those injected for joints
• Thiazide diuretics – at doses > 25 mg/day