Table 3.
American guidelines* regarding basal and premix insulin for type 2 diabetes mellitus.
| Recommendations | ADA 2001-2010ᵃ [ 17 - 27 ] | ADA 2011-2015b [ 28 - 33 ] | ADA 2016-2020 [ 34 - 38 ] | ADA - 2021 [ 39 ] |
AACE 2001-2020
[ 40 , 41 ] |
AACE/ACE 2009 - 2020 [ 42 - 46 ] |
|---|---|---|---|---|---|---|
| Timing of insulin initiation | Early initiation of insulin would be a safer approach for individuals presenting with weight loss, more severe symptoms, and glucose values >250-300 mg/dl | In patients with newly diagnosed type 2 diabetes and markedly symptomatic and/or elevated blood glucose levels or HbA1c, consider initiating insulin therapy (with or without additional agents) | The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when HbA1c levels (>10% [86 mmol/mol]) or blood glucose levels (≥300 mg/dL [16.7 mmol/L]) are very high | The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when HbA1c levels (>10% [86 mmol/mol]) or blood glucose levels (≥300 mg/dL [16.7 mmol/L]) are very high | For HbA1c level >9.0% and asymptomatic - try dual or triple therapy before initiating insulin; for symptomatic patients initiate insulin with/without other agents. For HbA1c level ≥7.5% to 9.0% - try dual therapy (if dual therapy is not useful) for 3 months followed by triple therapy for 3 months before initiating insulin | Insulin to be initiated among patients with HbA1c level >8.0% uncontrolled with dual or triple oral agents |
| Number of OADs to be used before initiating insulin | Although three oral agents can be used, initiation and intensification of insulin therapy is preferred based on effectiveness and expense | If the HbA1c target is not achieved after 3months of metformin monotherapy, consider one of the five treatment options combined with metformin: a sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 receptor agonist, or basal insulin | If noninsulin monotherapy at maximum tolerated dose does not achieve or maintain the HbA1c target after 3 months, add a second oral agent, a glucagon-like peptide 1 receptor agonist, or basal insulin | If the HbA1c target is not achieved after approximately 3 months, metformin can be combined with any one of the preferred six treatment options: sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor,GLP-1 RA, or basal insulin; the choice of which agent to add is based on drug-specific effects and patient factors | For HbA1c level >9.0% and asymptomatic - try dual or triple therapy before initiating insulin; for symptomatic patients initiate insulin with/without other agents. For HbA1c level ≥7.5% to 9.0% - try dual therapy (if dual therapy is not useful)for 3 months followed by triple therapy for 3 months before initiating insulin | 2 or 3 |
| Choice of initial insulin | - | Basal insulin considered as the most convenient regimen | Basal insulin considered as the most convenient regimen | Basal insulin considered as the most convenient regimen | Basal, basal-bolus, prandial, or premixed regimen | Preference changed from basal, basal-bolus, prandial, or premixed regimen in 2009 to basal insulin from 2016 onwards |
| Basal Insulin | - | - | - | - | Long-acting basal insulin is the initial choice for initiation of insulin therapy | - |
| Premixed/other insulin regimens | No specific recommendations | Twice daily premix insulin suggested as an option with less flexible dosing (2012 ADA EASD guideline) | - | - | Premix preferred in patients with adherence issues | - |
| Dose of insulin at initiation | 10 units or 0.2 U/kg | 10 units or 0.2 U/kg | 10 units per day or 0.1-0.2 units/kg/day, depending on the degree of hyperglycemia | 10 units per day or 0.1-0.2 units/kg/day, depending on the degree of hyperglycemia | Basal insulin: 0.1-0.2 U/kg/day if HbA1c <8% 0.2-0.3 U/kg/day if HbA1c >8% Premix insulin: Administered at the largest meal once daily or at the 2 largest meals twice daily |
Basal insulin: 0.1-0.2 U/kg if HbA1c <8%; 0.2-0.3 U/kg if HbA1c is >8% |
| Dose titration | Increase daily by 2 units every 3 days till the glycemic goals are achieved | Adjust by 10-15% or 2-4 U once-twice weekly | Adjust by 10-15% or 2-4 U once-twice weekly | Increase 2 U every 3 days | Titrate 2 U/day every 2-3 days until glycemic goals are reached | Insulin titration every 2-3 days by 2 U to reach glycemic goal |
| Dose intensification | Larger increments - 4 units every 3 days, can be followed if fasting glucose is >180 mg/dL | Add 1 rapid insulin injection before meal; if not controlled, consider basal-bolus Alternatively, change to premix insulin twice daily |
Add 1 rapid insulin injection before meal; if not controlled, consider basal-bolus Alternatively, change to premix insulin twice daily |
Add prandial insulin at 4 IU/day or 10% of the basal insulin If HbA1c above target, consider stepwise addition of prandial insulin OR self-mixed or split insulin regimen OR twice daily premix insulin regimen |
Prandial therapy with GLP-1 receptor agonist, SGLT2 inhibitor, DPP-4 inhibitor or prandial insulin (0.3-0.5 U/kg) | Consider adding GLP1-RA/SGLT2i/DPP4i OR prandial insulin for intensification |
Note: *Grade of evidence has been specified in italics wherever available. aIncludes ADA consensus statements for 2006 and 2009; bIncludes ADA-EASD 2012 guideline.
ADA: American Diabetes Association; AACE: American Association of Clinical Endocrinology; ACE: American College of Endocrinology; DPP4i: Dipeptidyl peptidase-4 inhibitor; FPG: Fasting plasma glucose; GLP1-RA: Glucagon-like peptide-1 receptor agonists; OAD: Oral antidiabetic drug; SGLT2i: Sodium/glucose cotransporter-2 inhibitor; TZD: Thiazolidinediones.