Liquid Meal Study With Insulin Lispro With/Without Recombinant Human Hyaluronidase PH20 (rHuPH20) and Regular Human Insulin With rHuPH20 to Compare Pharmacokinetics, Postprandial Glycemic Response, and Optimal Insulin Dose in Participants With Type 2 Diabetes Mellitus (T2DM)

This is a single-center, Phase 2, randomized, double-blind, 3-way crossover meal study in participants with Type 2 Diabetes Mellitus (T2DM) to determine the optimum dose and compare the pharmacokinetics (PK) and postprandial glycemic response of Humalog alone, Humalog + recombinant human hyaluronidase PH20 (rHuPH20), and Humulin-R + rHuPH20 administered subcutaneously.

This study design was chosen to assess the differences between pharmacokinetic (PK) and pharmacodynamic (PD) parameters, including postprandial glycemic response, of Humalog + recombinant human hyaluronidase PH20 (rHuPH20), Humalog alone, and Humulin-R + rHuPH20 at optimal doses following a liquid meal.

Eligibility Criteria:
Inclusion Criteria:

* Male or female of age 18 to 70 years, inclusive
* Participants with Type 2 diabetes mellitus (T2DM) per World Health Organization criteria treated with basal and/or bolus insulin for ≥12 months.
* Body mass index (BMI) between 18 to 45 kilograms per square meter (kg/m\^2), inclusive
* Glycosylated hemoglobin A1c (HbA1c) ≤10%
* Current treatment with insulin ≥60 Units/day (U/d)
* A participant taking oral hypoglycemic agents must be on a stable dose for \>8 weeks with the exception of thiazolidinediones (TZD), which should be \>12 weeks.
* Total body weight \>65 kilograms (kg) (143 pounds \[lb\]) for men and \>46 kg (101 lb) for women
* Vital signs (blood pressure \[BP\], pulse rate, and body temperature) within normal range or, if out of range, assessed by the Investigator as not clinically significant (NCS)
* Participants should be in good general health based on medical history and physical examination without medical conditions that might prevent the completion of study drug injections and assessments in this protocol
* Decision making capacity and willingness to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures including adequate venous access.
* Signed and written Internal Review Board-approved informed consent

Exclusion Criteria:

* Known or suspected allergy to any components of any of the study drugs in this study
* Previous enrollment in this study
* A participant who has proliferative retinopathy, proliferative maculopathy, and/or severe neuropathy (in particular, autonomic neuropathy) as judged by the Investigator
* As judged by the Investigator, clinically significant active disease of the gastrointestinal, cardiovascular (including a history of arrhythmia or conduction delays on electrocardiogram \[ECG\] and New York Heart Association \[NYHA\] Class III/IV heart disease), hepatic, neurological, renal, genitourinary, or hematological systems
* As judged by the Investigator, uncontrolled hypertension (diastolic BP ≥100 millimeters of mercury \[mmHg\] and/or systolic BP ≥160 mmHg after 5 minutes in the supine position).
* As judged by the Investigator, clinically significant findings in routine laboratory data (anemia with hematocrit less than 33% at screening is specifically exclusionary)
* Positive human immunodeficiency virus (HIV) antibody test, hepatitis B (anti-HBsAg), or hepatitis C (anti-HCV) antibody test
* Current addiction to alcohol or substances of abuse as determined by the Investigator
* Known use of drugs (other than oral hypoglycemic agents) that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action, glucose utilization, or recovery from hypoglycemia
* Recurrent major hypoglycemia or hypoglycemic unawareness as determined by the Investigator
* Mental incapacity, unwillingness, or language barriers precluding adequate understanding or cooperation in this study
* Symptomatic gastroparesis
* Donation of blood in excess of 500 milliliters (mL) within 56 days before dosing
* Use of any investigational drug or device 30 days before enrollment in this study
* Pregnancy, breast-feeding, the intention of becoming pregnant, or not using adequate contraceptive measures (adequate contraceptive measures consist of sterilization, intra-uterine device \[IUD\], oral or injectable contraceptives, barrier methods, or remaining abstinent)
* Any condition (intrinsic or extrinsic) that, in the judgment of the Investigator, will interfere with study participation or evaluation of data