Difference between revisions of "Diabetes mellitus type 2 Glycemic control"

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{{Diabetes mellitus type 2}}
{{Diabetes mellitus type 2}}
See also [[Glycemic Targets in Diabetes]]
Glycemic control is an important measure in diabetes treatment. There are general rules for glycemic control but they should be individualized for every patients based on provider decision and patient condition.
Glycemic control is an important measure in diabetes treatment. There are general rules for glycemic control but they should be individualized for every patients based on provider decision and patient condition.

Revision as of 14:04, 15 February 2020

Diabetes mellitus main page

Diabetes mellitus type 2 Microchapters


Patient information


Historical Perspective



Differentiating Diabetes Mellitus Type 2 from other Diseases

Epidemiology and Demographics

Risk Factors


Natural History, Complications and Prognosis


Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings


Chest X Ray



Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies


Medical therapy

Life Style Modification
Glycemic Control


Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Seyedmahdi Pahlavani, M.D. [2]

See also Glycemic Targets in Diabetes


Glycemic control is an important measure in diabetes treatment. There are general rules for glycemic control but they should be individualized for every patients based on provider decision and patient condition.

Measuring glycemic control

  • Hb A1C reflects average glycemia over approximately 3 months and has strong predictive value for diabetes complications.[1][2] Therefore, A1C should be measured as baseline control and every 3 month to see whether the treatment goals have been achieved and maintained.
  • Blood glucose, via self monitoring of blood glucose (SMBG) is accurate and easy to use by patients. It allows patients to evaluate their individual response to therapy and assess whether glycemic targets are being achieved. SMBG is mostly used for patients with type 1 diabetes mellitus but some patients with type 2 diabetes who require basal insulin will benefit from this method of monitoring. The following video shows how to apply glucometer devices for SMBG.


Evidence from trials

Forest Plot showing meta-analysis of randomized controlled trials of differing target glucose control and mortality for diabetes mellitus type 2. Note the heterogeneity due to increased death when the glycosylated hemoglobin A (Hb A1c) target was 6.0% in the ACCORD trial

A goal fasting blood glucose of below 108 mg/dl (6 mmol/L) over 10 years resulting in an Hb A1c of 7% over 10 years was found in the United Kingdom Prospective Diabetes Study (UKPDS 33) randomized controlled trial. Intensive control reduced diabetic complications in one out of every 20 patients (number needed to treat = 20).[3]

A goal fasting blood glucose of below 108 mg/dl (6 mmol/L) over 10 years resulting in an Hb A1c of 7.4% over 10.7 years in the metformin group compared to 8.0% in the conventional group in the UK Prospective Diabetes Study (UKPDS 34) randomized controlled trial. Metformin reduced cardiovascular disease in one out of every 11 patients (number needed to treat = 11).[4]

A Hb A1c of 6.9% over 6 years was found in the VA Diabetes Trial (VADT) randomized controlled trial to have no significant effect on diabetic complications.[5] Although the treatment group averaged an Hb A1c of 6.9%, the goal was 6.0%.[6]

A Hb A1c goal of 6.5% over 5 years was found in the ADVANCE randomized controlled trial not to reduce mortality using a protocol whose first step was a sulfonylurea (gliclazide). The intervention group had 0.9% less nephropathy, but more severe hypoglycemia.[7]

A Hb A1c goal of 6% over 3.5 years was found in the ACCORD randomized controlled trial found to increase serious complications.[8][9]

The ORIGIN trial used basal insulin supplementation to reduce the Hb A1c from 6.4% to 6.2%. There was no benefit on cardiac outcomes but there was an increase in hypoglycemia and weight gain.[10]

The PROACTIVE study used pioglitazone.[11]

The older University Group Diabetes Program (UGDP) also found no benefit in a controversial randomized controlled trial.[12][13][14][15][16] The UGDP randomized approximately 1000 patients to one of five treatment groups and followed from 1962 to 1975: phenformin, tolbutamide, small fixed-dose insulin (ISTD) based on body-surface area (averaged 14 units per day), variable-dose insulin (ISTD) (averaged 45 units per day), n (IVAR), or placebo. The trial found statistically significant increase in cardiovascular deaths among the patients treated with tolbutamide and so this group was stopped in 1969. The phenformin group was also stopped early due to increased mortality. The ISTD group had no reduction in blood glucose. The IVAR group had a reduction in the IVAR group of about 2.0 mmol/L (36 mg/dL) which correlates to a 1% difference in the level of Hb A1c.[17] Problems in the trial include: 1) "25% of placebo and tolbutamide-treated subjects dropped out or changed medication during the trial[14], 2) glucose values were only checked quarterly[15], 3) smoking history was not measured[15] 4) reduced fraction of males in the IVAR group (IVAR=22%; placebo=31%).

Clinical Practice Guidelines

There are opposing guidelines between the American College of Physicians (ACP) and the American Diabetes Association (ADA) on the goal for the HbA1c. Taking these guidelines into consideration, what is both an evidence-based and clinically practical HbA1c goal?​

The American College of Physicians published clinical practice guidelines in 2018 that states[18]:

  • "clinicians should aim to achieve an HbA1c level between 7% and 8% in most patients with type 2 diabetes...and should consider de-intensifying pharmacologic therapy in patients with type 2 diabetes who achieve HbA1c levels less than 6.5%."

The American Diabetes Association published clinical practice guidelines in 2019[19] and released a response statement in opposition to the ACP's guidelines:

  • "The ADA recommends that a reasonable A1C goal for many nonpregnant adults with type 2 diabetes is less than 7 percent based on the available evidence to date from the ACCORD, ADVANCE, VADT and UKPDS international clinical trials, which were evaluated and incorporated into ADA’s Standards of Care."[20]
  • Preprandial capillary plasma glucose should be ranged between 80 mg/dL (4.4 mmol/L) up to 130 mg/dL (7.2 mmol/L).​
  • Peak postprandial capillary plasma glucose which is measured 1-2 hours after the beginning of the meal should be kept less than 180 mg/dl (10 mmol/L)​

Kaiser Permanente states[21]:

  • A1C goal of 7.0–8.0%
  • "Use clinical judgment to determine if a target lower than 7.0% is appropriate for an individual patient. It can be challenging to push a patient’s HbA1c levels from just above 7.0% to below 7.0%. There are potential benefits (decreased nonfatal myocardial infarction) and potential harms (hypoglycemia, weight gain, and possible increase in all-cause and cardiovascular-cause mortality) of intensive glucose therapy, especially in patients with known cardiovascular disease."
  • "For frail elderly patients, a target HbA1c of 7.0–9.0% is reasonable"

Frequency goals are achieved

Typical practice:

  • 35% of patients have an HbA1c of less than 7 per HEDIS measures[22]:
  • 59% according to NHANES (self-reported by patients[23])[24]

Best practice

  • 71% in the Veterans Affairs VISN16[25].
  • 69% according to Kaiser in Colorado[26] However, this is the proportion of patients "ever achieving" goal and not clear is this is equivalent to a cross-section of patients at goal.


  1. Albers JW, Herman WH, Pop-Busui R, Feldman EL, Martin CL, Cleary PA, Waberski BH, Lachin JM (2010). "Effect of prior intensive insulin treatment during the Diabetes Control and Complications Trial (DCCT) on peripheral neuropathy in type 1 diabetes during the Epidemiology of Diabetes Interventions and Complications (EDIC) Study". Diabetes Care. 33 (5): 1090–6. doi:10.2337/dc09-1941. PMC 2858182. PMID 20150297.
  2. Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR (2000). "Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): prospective observational study". BMJ. 321 (7258): 405–12. PMC 27454. PMID 10938048.
  3. "Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group". Lancet. 352 (9131): 837–53. 1998. doi:10.1016/S0140-6736(98)07019-6. PMID 9742976. Review by ACP Journal Club
  4. "Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group". Lancet. 352 (9131): 854–65. 1998. PMID 9742977.
  5. Duckworth W, Abraira C, Moritz T; et al. (2009). "Glucose control and vascular complications in veterans with type 2 diabetes". N. Engl. J. Med. 360 (2): 129–39. doi:10.1056/NEJMoa0808431. PMID 19092145. Unknown parameter |month= ignored (help)
  6. Abraira C, Duckworth W, McCarren M; et al. (2003). "Design of the cooperative study on glycemic control and complications in diabetes mellitus type 2: Veterans Affairs Diabetes Trial". Journal of diabetes and its complications. 17 (6): 314–22. PMID 14583175.
  7. "Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes". N. Engl. J. Med. 358 (24): 2560–2572. 2008. doi:10.1056/NEJMoa0802987. PMID 18539916. Unknown parameter |month= ignored (help)
  8. Anonymous (February 6, 2008). "For Safety, NHLBI Changes Intensive Blood Sugar Treatment Strategy in Clinical Trial of Diabetes and Cardiovascular Disease -". National Institutes of Health (NIH). Retrieved 2008-02-07.
  9. Gerstein HC, Miller ME, Byington RP; et al. (2008). "Effects of intensive glucose lowering in type 2 diabetes". N. Engl. J. Med. 358 (24): 2545–59. doi:10.1056/NEJMoa0802743. PMID 18539917. Unknown parameter |month= ignored (help)
  10. The ORIGIN Trial Investigators (2012). "Basal Insulin and Cardiovascular and Other Outcomes in Dysglycemia". N Engl J Med. doi:10.1056/NEJMoa1203858. PMID 22686416.
  11. Dormandy JA, Charbonnel B, Eckland DJ, Erdmann E, Massi-Benedetti M, Moules IK; et al. (2005). "Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial". Lancet. 366 (9493): 1279–89. doi:10.1016/S0140-6736(05)67528-9. PMID 16214598. Review in: ACP J Club. 2006 Mar-Apr;144(2):34 Review in: Evid Based Med. 2006 Apr;11(2):47
  12. Meinert CL, Knatterud GL, Prout TE, Klimt CR (1970). "A study of the effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. II. Mortality results". Diabetes. 19: Suppl:789–830. PMID 4926376.
  13. "Effects of hypoglycemic agents on vascular complications in patients with adult-onset diabetes. VIII. Evaluation of insulin therapy: final report". Diabetes. 31 Suppl 5: 1–81. 1982. PMID 6757026.
  14. 14.0 14.1 Kilo C, Miller JP, Williamson JR (1980). "The Achilles heel of the University Group Diabetes Program". JAMA. 243 (5): 450–7. doi:10.1001/jama.1980.03300310038020. PMID 6985989.
  15. 15.0 15.1 15.2 Genuth S (1996). "Exogenous insulin administration and cardiovascular risk in non-insulin-dependent and insulin-dependent diabetes mellitus". Ann Intern Med. 124 (1 Pt 2): 104–9. PMID 8554200.
  16. Feinglos MN, Bethel MA (1999). "Therapy of type 2 diabetes, cardiovascular death, and the UGDP". Am Heart J. 138 (5 Pt 1): S346–52. doi:10.1016/S0002-8703(99)70034-7. PMID 10539796.
  17. Gaster B, Hirsch IB (1998). "The effects of improved glycemic control on complications in type 2 diabetes". Arch Intern Med. 158 (2): 134–40. PMID 9448551.
  18. Qaseem A, Wilt TJ, Kansagara D, Horwitch C, Barry MJ, Forciea MA; et al. (2018). "Hemoglobin A1c Targets for Glycemic Control With Pharmacologic Therapy for Nonpregnant Adults With Type 2 Diabetes Mellitus: A Guidance Statement Update From the American College of Physicians". Ann Intern Med. doi:10.7326/M17-0939. PMID 29507945.
  19. American Diabetes Association (2019). "6. Glycemic Targets: Standards of Medical Care in Diabetes-2019". Diabetes Care. 42 (Suppl 1): S61–S70. doi:10.2337/dc19-S006. PMID 30559232.
  20. Anonymous (2008). American Diabetes Association® Deeply Concerned About New Guidance from the American College of Physicians Regarding Blood Glucose Targets for People with Type 2 Diabetes
  21. Kaiser Permanente Care Management Institute. Guidelines. Available at http://kpcmi.org/how-we-work/guidelines/
  22. Anonymous (2017). Comprehensive Diabetes Care
  23. Anonymous (2016). NHANES Participant Homepage. CDC/National Center for Health Statistics
  24. Selvin E, Parrinello CM, Sacks DB, Coresh J (2014). "Trends in prevalence and control of diabetes in the United States, 1988-1994 and 1999-2010". Ann Intern Med. 160 (8): 517–25. doi:10.7326/M13-2411. PMC 4442608. PMID 24733192.
  25. Shi L, Ye X, Lu M, Wu EQ, Sharma H, Thomason D; et al. (2015). "Glycemic and Cholesterol Control Versus Single-Goal Control in US Veterans with Newly Diagnosed Type 2 Diabetes: A Retrospective Observational Study". Diabetes Ther. 6 (3): 339–55. doi:10.1007/s13300-015-0122-2. PMC 4575310. PMID 26202185.
  26. Schroeder EB, Hanratty R, Beaty BL, Bayliss EA, Havranek EP, Steiner JF (2012). "Simultaneous control of diabetes mellitus, hypertension, and hyperlipidemia in 2 health systems". Circ Cardiovasc Qual Outcomes. 5 (5): 645–53. doi:10.1161/CIRCOUTCOMES.111.963553. PMC 3590111. PMID 22851534.