Module 1
Summary of Brazilian Diabets Society Members Opinions on the New ADA/EASD Algorithm
ANSWERES' PERCENTAGES | |||
---|---|---|---|
PROPOSED QUESTIONS | Yes | No | Others |
1. Have you read the Treatment of Type 2 Diabetes algorithm proposed by ADA/EASD?
| 90 | 10 | - |
2. Were you aware that the document expresses the opinion of a few authors and not of the entities involved? | 77 | 23 | - |
3. Do you intend to adopt the stages and steps suggested by this algorithm in your practice? | 51 | 49 | - |
4. Do you think that rosiglitazone-associated adverse events have been ratified in the medical literature of excellence? | 36 | 64 | - |
5. Do you think that the cardiovascular protection assigned topioglitazone in that Position Statement is real? | 34 | 66 | - |
6. Do you think that glitazone-associated adverse events (bone fracture and cardiovascular events) are effects pertaining to this therapeutical class? | 49 | 21 | 30 |
7. Do you think that only GLP-1 analogs should be included in diabetes treatment excluding DPP-4 inhibitors? | 13 | 69 | 18 |
8. Do you think that BDS' members have the expertise and the ability of criticism to issue a Position Statement about this Algorithm? | 87 | 4 | 9 |
General conclusions about the survey results
Module 2
Results of the controversial diabetes argument acceptability assessment
Score | Acceptability Level | Interpretation |
---|---|---|
0 - 2 | 1 | Full rejection |
3 - 4 | 2 | Partial rejection |
5 - 6 | 3 | Neutrality |
7 - 8 | 4 | Partial acceptance |
9 - 10 | 5 | Full acceptance |
Average acceptability level of controversial matters assessed and their respective bibliographical references
Module 3
New SBD algorithm proposal for the treatment of type 2 diabetes
Laboratory goals for characterization of good glycemic control
Parameter | Laboratory Targets | |
---|---|---|
Desirable Levels | Tolerable Levels | |
Glycated hemoglobin (A1C) | <7% (in adults) | 7.5-8.5%: 0-6 years old1; <8%: 6-12 years old1; <7.5%: 13-19 years old1; 8%: in the elderly1,3 |
Fasting glycemia | <110 mg/dL | Up to 130 mg/dL2 |
Pre-prandial glycemia | <110 mg/dL | Up to 130 mg/dL2 |
Post-prandial glycemia | <140 mg/dL | Up to 180 mg/dL2 |
New SBD algorithm proposal for treating type 2 diabetes
STAGE 1: INITIAL CONDUCT ACCORDING TO CURRENT CLINICAL CONDITION | |||
---|---|---|---|
Mild manifestations | Moderate manifestations | Severe manifestations | Hospitalization if glycemic levels >300 mg/dL |
↓ | ↓ | ↓ | ↓ |
• Glycemic levels <200 mg/dL + • Mild symptoms or no symptoms + • Absence of other acute concomitant diseases | • Any glycemic levels between 200-300 mg/dL + • Absence of criteria for mild or severe manifestations | • Any glycemic levels above 300 mg/dL = Or = • Significant weight loss = Or = • Severe and significant symptoms = Or = • Presence of ketonuria | Under the following conditions: • Diabetic ketoacidosis and hyperosmolar state = Or = • Intercurrent severe disease or comorbidity |
↓ | ↓ | ↓ | ↓ |
Metformin (500 mg/day, intensifying up to 2,000 mg/day) + lifestyle changes. If patient does not reach A1C<7% in 4-6 weeks → Note: In case of metformin intolerance, prolonged action formulations may be useful. If the problem persists, choose one of the options in Step 2 | Metformin (500 mg/day, intensifying up to 2,000 mg/day) + lifestyle changes + other oral antidiabetic drugs CRITERIA FOR INCLUDING SECOND OAD ↓ | Start insulin therapy immediately | Start therapy according to the algorithm recommendations and to glycemic control obtained after discharge from hospital |
STAGE 2: ADD OR MODIFY SECOND AGENT ACCORDING TO A1C LEVEL(*)
| |||
7- 8%
|
8-10%
|
>10%
| |
Sulphonylurea DPP-4 inhibitors Glitazone Glinides (prevalent post-prandial hyperglycemia) Acarbose (prevalent post-prandial hyperglycemia) Exenatide (overweight or obesity) | Sulphonylurea DPP-4 inhibitors Glitazone Basal insulin (bedtime) Exenatide (overweight or obesity) | Insulin therapy Basal insulin + prandial insulin With of without Metformin Sulphonylurea iDPP-4 (studies currently being made) | |
(*) In order to select the second agent, we suggest looking at therapeutic drug profiles in table 7. | |||
MONITORING AND ADJUSTMENTS IN TREATMENT AFTER 2-3 MONTHS WITH MAXIMUM EFFECTIVE DOSAGE IN ORDER TO REACH GOALS: A1C<7%, FASTING GLYCEMIA <130 mg/dL OR POST-PRANDIAL GLYCEMIA (2 HOURS) <180 mg/dL
| |||
STAGE 3: ADD A THIRD ORAL AGENT OR INTENSIFY INSULIN TREATMENT
| |||
↓ | ↓ | ||
Add a third oral agent with a different action mechanism. If in 2 or 3 months the targets of A1C<7%, fasting glycemia <130 mg/dL or post-prandial glycemia (2 hours) <180 mg/dL are not reached, start insulin therapy. → | Intensify insulin therapy until the A1C<7%, fasting glycemia<130 mg/dL or post-prandial glycemia (2 hours) <180 mg/dL goals are reached. | ||
INSTRUCTIONS AND ADDITIONAL COMMENTS | |||
1.Similarly to any other Guideline, this Algorithm contains general recommendations about the most highly indicated therapeutic options for each clinical situation. The choice of the best therapeutical plan must be made based on medical judgment, in patient's options and in treatment costs with the respective drugs. | |||
2.For further information on the potential of A1C level reduction of different drugs, please refer to table 6, in Module 4. | |||
3.For further summarized information on therapeutic and usage safety profile of several drugs, please refer to table 7, in Module 4. | |||
Abbreviations: | |||
A1C = glycated hemoglobin; inhibitors ofDPP-4 (dipeptidyl peptidase-4 ); OAD = oral antidiabetic drugs. |
Module 4
Summary of therapeutic profile of drugs used for treating type 2 diabetes
Comparative efficacy and potential of A1C reduction of different therapeutic interventions
Strategy/Drug | Expected Reduction in A1C (%) |
---|---|
Weight reduction and increase in physical activity | 1.0 - 2.0 |
Metformin | 1.0 - 2.0 |
Insulin as additional therapy | 1.5 - 3.5 |
Sulfonylurea | 1.0 - 2.0 |
Glitazones | 0.5 - 1.4 |
GLP1 Agonists | 0.5 - 1.0 |
DPP-4 Inhibitors | 0.5 - 0.8 |
Alpha-glycosidase Inhibitors | 0.5 - 0.8 |
Glinides | 0.5 - 1.5 |
Summary of therapeutic profiles of drugs used for treating type 2 diabetes
DRUG | PROFILE AND ACTION MECHANISM |
---|---|
Acarbose (Glucobay®) | Slows down intestinal glucose absorption. Low potential of A1C reduction (0.5 - 0.8%). Gastrointestinal intolerance. |
Metformin (Glifage®, others) | Reduces primarily the hepatic glucose production and fights insulin resistance. High potential of A1C reduction (2%). Gastrointestinal intolerance. Does not cause hypoglycemia. May promote mild weight loss. Contraindicated in case of renal dysfunction. |
Glitazones - Rosiglitazone (Avandia®) - Pioglitazone (Actos®) | Primarily fight insulin resistance and reduces hepatic glucose production. Increases muscle, fatty tissue and liver sensitivity to insulin. Intermediate A1C reduction potential (0.5 - 1.4%). Promote hydric retention and weight gain, increasing the risk of heart failure. Also increase the risk of fracture. Recent results of studies such as RECORD and BARI 2D indicate that rosiglitazone does not increase the risk of infarction and CVD. |
Sulfonylureas - Glimepiride (Amaryl®) - Glibenclamide (Daonil®) - Gliclazide (Diamicron MR®) - Others | Stimulate endogenous insulin production by pancreatic beta cells, with pharmacological action medium to long (8-24 hours). Useful to control fasting glycemia and 24-hour glycemia. High potential of A1C reduction (2%). May cause hypoglycemia. Glibenclamide has higher risk of hypoglycemia. An alleged deleterious action on human beta cells has not yet been confirmed. |
Glinides - Repaglinide (Novonorm®, Prandin®) - Nateglinide (Starlix®) | Stimulate endogenous insulin production by pancreatic beta cells, with short duration (1-3 hours). Useful to control post-prandial hyperglycemia. Intermediate potential of A1C reduction (1.0 - 1.5%). May promote weight gain and hypoglycemia. Repaglinide is more powerful than nateglinide. |
Incretin mimetics and DPP-4 inhibitors - Exenatide (Byetta®) - Vildagliptin (Galvus®) - Sitagliptin (Januvia®) | This is a new therapeutic class for treating diabetes, whose mechanism includes stimulating beta cells to increase insulin synthesis and action on pancreatic alpha cells, reducing glucagon production. Glucagon has the effect of increasing glycemic levels. Average potential of A1C reduction (0.5 - 0.8%, depending on the basal A1C value). Do not cause hypoglycemia but gastrointestinal intolerance and pancreatitis have been described (exenatide and sitaglipitn) [13, 14]. |
Fixed combinations of oral antidiabetic drugs
Therapeutic classes | Chemical Denomination | Commercial Denomination | Action and Dosage Mechanism |
---|---|---|---|
sulffonylurea + biguanide | glimepiride + metformin | Amaryl Flex® Sanofi-Aventis | Long acting secretagogue of insulin (glimepiride) + peripheral action insulin sensitizer (metformin). Dosage: glimepiride - 1 mg and 2 mg + metformin - 500 mg. |
glinide + biguanide | nateglinide + metformin | Starform® Novartis | Short-acting secretagogue of insulin (nateglinide) + peripheral action insulin sensitizer (metformin). Dosage: nateglinide - 120 mg + metformin - 500 mg and 850 mg. |
Therapeutic classes | Chemical Denomination | Commercial Denomination | Action and Dosage Mechanism |
---|---|---|---|
biguanide + sulphonylurea | metformin + glibenclamide | Glucovance® Merck | Peripheral action insulin sensitizer (metformin) + long-acting secretagogue of insulin (glibenclamide). Dosage: 250 mg metformin+1.25 mg glibenclamide 500 mg metformin + 2.5 mg glibenclamide 500 mg metformin + 5 mg glibenclamide. |
glitazone + biguanides | rosiglitazone + metformin | Avandamet® Glaxo | Combination of two peripheral action insulin sensitizers, with different action Dosage: 2 mg rosiglitazone + 500 mg metformin 4 mg rosiglitazone + 500 mg metformin. |
Incretin mimetic + metformin | sitagliptin + metformin | Janumet® MSD | DPP-4inhibitor + peripheral action insulin sensitizer (metformin). Dosage: 50 mg sitagliptin + 500, 850 or 1,000 mg metformin |
Incretin mimetic + metformin | vildagliptin + metformin | Galvus Met® Novartis | DPP-4 inhibitor + peripheral action insulin sensitizer (metformin). Dosage: 50 mg vildagliptin + 500, 850 or 1,000 mg metformin |
Action profile of human insulin and human insulin analogs
Human Insulins | Insulin Type | Onset | Action peak | Duration of action |
---|---|---|---|---|
Rapid-acting insulin analogs
| Glulisine (Apidra®) | <5-15 minutes | 1 hour | 4 hours |
Lispro (Humalog®) | <15 minutes | 0.5-1.5 hour | 2-4 hours | |
Aspart (NovoRapid®) | 5-10 minutes | 1-3 hours | 3-5 hours | |
Short acting insulin
| Regular (Novolin® R, Humulin® R) | 30-60 minutes | 2-3 hours | 3-6 hours |
Intermediate acting insulin
| NPH (Novolin® N Humulin® N) | 2-4 hours | 4-10 hours | 10-16 hours |
Long-acting insulin analogs
| Glargine (Lantus®) | 1-2 hours | None | Up to 24 hours |
Detemir (Levemir®) | 1-2 hours | None | Up to 24 hours |
Insulin aspart and protaminated (70%) + insulin aspart (30%) | NovoMix® 70/30 | Pre-mix with 70% long-acting insulin aspart (up to 24 hours) + 30% aspart insulin of immediate release, short acting (4-6 hours), to control post-prandial and interprandial glycemic levels |
Neutral protamine insulin lispro (75%) + insulin lispro (25%) | Humalog® Mix 25 | Pre-mix with 75% intermediate acting insulin NPL (up to 24 hours) + 25% insulin of immediate release, short-acting (4-5 hours), to control post-prandial and interprandial glycemic levels |
Neutral protamine insulin lispro (50%) + insulin lispro (50%) | Humalog® Mix 50 | Pre-mix with 50% intermediate acting insulin NPL (up to 24 hours) + 50% insulin of immediate release, short-acting (4-5 hours), to control post-prandial and interprandial glycemic levels |