Insulinoterapia

Luis Antonio Rodríguez.

Fellow-Endocrinología clínica y
metabolismo
2020
1909, Jean de Mayer named the yet undiscovered glucose-
controlling substance insulin.
 PN: 1923 a los 32 años

Leonard Thompson-Enero de 1922.

 110 aminoácidos.

-24 aminoácidos.

81 aminoácidos.

-31 aminoácidos.
-4 aminoácidos.

51 aminoácidos.
Brazo corto del cromosoma 11 (11p15.5)
Experimental & Molecular Medicine (2016) 48, e219
Lodish, Berk, kaiser, et al. Molecular Cell Biology. 8th Ed. 2016. pp 708-176
Nature. 2001; 414(6865): 799–806.
 INSULINORESISTENCIA
A subnormal biological response to endogenous and/or exogenous insulin.
Nature Medicine volume12, pages41–42 (2006)
Atención Familiar. 2017; 24: 136-9.
Diabetes Care 2016;39:179–186
Diabetes Care 2016;39:179–186
 Time-Line

Diabetes Care 2016;39:179–186

Diabetes Care 2016;39:179–186
 Ácido Hexadecandioico

NATURE REVIEWS ENDOCRINOLOGY. 2017. doi:10.1038/nrendo.2017.39

NATURE REVIEWS ENDOCRINOLOGY. 2017. doi:10.1038/nrendo.2017.39
NATURE REVIEWS ENDOCRINOLOGY. 2017. doi:10.1038/nrendo.2017.39
 Zinc e Insulinoresistencia

NATURE REVIEWS ENDOCRINOLOGY. 2017. doi:10.1038/nrendo.2017.39

Control metabólico Hipoglucemia
• 5102newly diagnosed drug-naive DM.
• intensive glucose control with a
sulfonylurea or insulin.
• Management with diet alone.
• Median 10.7 years.

Lancet. 1998;352:837853.
 The DCCT randomly assigned 1441
patients with type 1 diabetes to intensive
or conventional therapy: USA-Canada.

N Engl J Med 2008; 358:2545-2559

Ann Intern Med. 2019;171:505-513.
Diabetes Care 2010;33:983990.
American Journal of Therapeutics 0, 1–12 (2019)
American Journal of Therapeutics 0, 1–12 (2019)
n engl j med. 2017. 377;6: 573.
Diabetes Care Volume 43, Supplement 1, January 2020
Diabetes Care Volume 43, Supplement 1, January 2020
Diabetes Care Volume 43, Supplement 1, January 2020
 • 17374 patients.
• Study of Once Daily Levemir was a 24-week
international observational study involving 10 countries

Nearly half of the patients had HbA1c ≥9.0% Median time to initiation of insulin therapy
despite prolonged treatment with multiple OADs. was 7.7 years
 Clinical inertia in the management of type 2
diabetes mellitus: a focused literature review

Br J Diabetes Vasc Dis 2015;15:65-69

 P/Pacientes adultos con DM tipo 2.
I/ Las intervenciones con múltiples insulinas
O/ Eficacia (cambio en el nivel de hemoglobina A1c [HbA1c] desde el inicio [resultado
primario]; porcentaje de pacientes con nivel de HbA1c <7% al final del estudio y
cambio en el peso corporal [resultados secundarios]) y seguridad (hipoglucemia) de
los análogos de insulina basal.
S/Ensayos controlados aleatorios de al menos 12 semanas de duración,
independientemente del diseño del estudio (paralelo o cruzado) o los outcomes
informados.

Ann Intern Med. 2018;169:165-174.

Ann Intern Med. 2018;169:165-174.
Ann Intern Med. 2018;169:165-174.
Vida ultraprolongada
Gracias
Diabetes Care Volume 43, Supplement 1, January 2020
Diabetes Care Volume 43, Supplement 1, January 2020
Diabetes Care Volume 43, Supplement 1, January 2020
Estrategias de titulación
 T2T trial designs

force-titrate
Compare insulin dosages to
investigational vs achieve a
standard insulin. prespecified
treatment goal.

US Food and Drug Administration. 2008. Center for Drug Evaluation and Research. Guidance for Industry. Diabetes Mellitus: Developing Drugs and Therapeutic Biologics for Treatment and
Prevention. Available from URL: http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatory Information/Guidances/ucm071624.pdf.
Diabetes, Obesity and Metabolism. 2014; 16: 193–205.
 P: 756 overweight patients with inadequate glycemic control
(HbA1c 7.5%) on one or two oral agents.

I: bedtime glargine once daily.

C: bedtime NPH once daily.

O: Compare the abilities and associated hypoglycemia risks

Randomized,
• added
of insulins to OAD inopen-label,
T2D to achieveparallel.
7% HbA1c.
• 24- week multicenter trial.
Titrated using a simple algorithm
seeking a target FPG: <100 mg/dl.
Diabetes Care 26:3080–3086, 2003
 Insulin dosage: Higher with glargine
• 80 sites in the U.S.thanand withCanada.
NPH: Week 2 until the study’s
end (P: 0.05–0.001).
• 7 January 2000 and 22 Octobercriteria:
Exclusion 2001.
• Prior insulin except (GD or for 1 week.
• Inclusion criteria: BMI • Current use of an -glucosidase inh or a
between 26 and 40 kg/m2. rapid-acting
Meaninsulin
DD: secretagogue,
Glargine: 47.2 +/-use1.3
of IU
• HbA1c between 7.5 and 10.0%. vs. NPH:
other agents 41.8 +/-
affecting 1.3. (Pcontrol,
glycemic 0.005; tx
history ofdifference 5.3 IU
ketoacidosis or [95% CI 1.8 – 8.9]).
self-reported
• FPG 140 mg/dl (7.8 mmol/l).
inability to recognize hypoglycemia,
ALT/AST >2 above the ULN or sCr (1.5
mg/dlWeight
for menincreased:
and 1.4 mg/dl for0.2
3.0 +/- women).
kg
• Drug or alcoholvs
-Glargine abuse or inability
2.8 +/- to
0.2 kg-NPH.
provide informed consent.
• Risk of LADA.
Diabetes Care 26:3080–3086, 2003
 T2T trial: Glargine - Determir

Diabetes, Obesity and Metabolism. 2014; 16: 193–205.

Diabetes Care 29:1269 –1274, 2006
 Multinational, randomised, open-label,
parallel-group, non-inferiority trial.

Diabetologia (2008) 51:408–416

 T2T trial: Glargine - Determir

Diabetologia (2008) 51:408–416

 T2T trial: Glargine - Degludec

Diabetes 2011; 60(Suppl 1): A20.

 T2T trial: Glargine - Degludec

Diabetes 2011; 60(Suppl 1): A20.

 • 1-year, parallel-group.
• Randomized, open-label, treat-to-target trial.
• 1 September 2009 and 17 January 2011.
• Conducted at 166 sites in 12 countries

Diabetes Care 35:2464–2471, 2012

P: insulin-naïve Adults with T2D
with A1C of 7-10% taking OADs.

I: Daily Degludec (733)

C: Daily Glargine (257)

O: Evaluate safety and efficacy.

Diabetes Care 35:2464–2471, 2012

• A1C < 7% without hypoglycemia:
• (42 and 46%, P = 0.34).
• Similar DID: Ideg: 0.59 units/kg Iglar: 0.60 UI/kg.

Mean weight gain was similar (3.6 vs. 4.0 kg).

Diabetes Care 35:2464–2471, 2012

 • 52 week, parallel-group.
• Randomized, phase 3, open-label, T2T,
non-inferiority trial.
• 1 September 2009 and 28 October 2010.
• Conducted in 123 sites in 12 countries

Lancet. 2012; 379: 1498–507

 P: Adults with T2D with A1C of 7-
10% with insulin ± oral agents .

I: Daily Degludec (755) In combination with insulin aspart

before meals with or without
C: Daily Glargine (251) metformin and/or pioglitazone.

O: Evaluate safety and efficacy. Insulin was titrated to achieve a

breakfast FPG level of 70–90 mg/dl.

Lancet. 2012; 379: 1498–507

Lancet. 2012; 379: 1498–507
 (A) Overall confirmed hypoglycaemic episodes. (B) Nocturnal confi rmed hypoglycaemic episodes. (C) Diurnal confi rmed
hypoglycaemic episodes. (D) Cumulative number of hypoglycaemic episodes per participant during 24 h.

Lancet. 2012; 379: 1498–507

BMJ Open Diabetes Res Care. 2019 Oct 1;7(1):e000679.
 3 categories of trials were analyzed:

• T1DMB/B.
• T2DMinsulin-nave.
• T2DMB/B.

Diabetes Ther (2014) 5:435–446

Diabetes & Metabolism 44 (2018) 402–409
 A number of titration algorithms have
been evaluated that aim to simplify insulin
titration and empowerment self-titration.

Diabetes Spectrum, ds180005. doi:10.2337/ds18-0005 

Adv Ther (2019) 36:1031–1051
 Are short-acting insulin analogues more useful than
regular human insulin for adults with type 1 diabetes?

Cochrane Database of Systematic Reviews 2016, Issue 6. Art. No.: CD012161.

Endocr Pract. 2019 Sep;25(9):935-942.
P

O
• Revisiones de análogos de primera y segunda generación.
Diabetes Obes Metab. 2019;10.1111/dom.13936.
Current Diabetes Reports. 2019; 19:14: 1-7.
Hipoglucemia: insulinoterapia.
Estrategias de manejo.
Monitoreo Flash.
Diabetes gestacional
Diabetes y glucocorticoides